Janne Elin Reseland

• Süslü, Safiyye; Haugen, Håvard Jostein; Krüger, Tormod Bjartveit; Reseland, Janne Elin & Herlofson, Bente Brokstad (2026). Medication-related osteonecrosis of the jaw in cancer and osteoporosis patients: a retrospective seven-year single-center Norwegian cohort study of clinical profiles and documented soft tissue healing. Acta Odontologica Scandinavica. ISSN 0001-6357. 85, p. 713–724. doi: 10.2340/aos.v85.46983. Full text in Research Archive Show summary

  Objective: To compare systemic profiles, oral findings, and documented soft tissue healing between cancer and osteoporosis patients with medication-related osteonecrosis of the jaw (MRONJ). Material and methods: This retrospective single-center cohort included 105 cases treated in 2013–2019 (56 cancer; 49 osteoporosis). Healing at last follow-up was analyzed using adjusted logistic regression and Firth sensitivity analysis. Results: Of 102 cases with known final status, 68 had documented healing. Osteoporosis cases were older, predominantly female, and had longer antiresorptive exposure than cancer cases (76.7 ± 11.1 vs. 70.0 ± 8.5 years; 102.5 ± 77.8 vs. 34.6 ± 28.5 months; both p < 0.001). Stage II predominated and Stage 0 was uncommon (3/105, 2.9%). Previous tooth extraction at the MRONJ lesion site was more frequent in osteoporosis (95.9% vs. 71.4%; p < 0.001). Surgical treatment was associated with higher healing odds (adjusted odds ratio [OR]: 11.12, 95% confidence interval [CI]: 4.12 to 33.35; p < 0.001), whereas cancer indication was associated with lower odds (adjusted OR: 0.23, 95% CI: 0.07 to 0.68; p = 0.011). Conclusions: Systemic profiles differed; oral patterns were similar. Non-random treatment and missing healing dates limit interpretation. Previous tooth extraction was the most frequent antecedent event; its indication and timing were unverified.

• Reppe, Sjur; Nogueira, Liebert Parreiras; Yu, Fangtang; Valland, Haldor; Gautvik, Vigdis Teig & Utheim, Tor Paaske [Show all 9 contributors for this article] (2026). Integrated analysis of human osteocyte lacunar ultrastructure and bone proteome profiling reveals coupling between immune and osteogenic signaling pathways. Bone. ISSN 8756-3282. 213. doi: 10.1016/j.bone.2026.118077.
• Süslü, Safiyye; Haugen, Håvard Jostein; Krüger, Tormod Bjartveit; Herlofson, Bente Brokstad; Reseland, Janne Elin & Eriksen, Erik Fink (2026). Oral findings and antiresorptive therapy exposure duration in postmenopausal women with osteoporosis: a cross-sectional cohort study. BMC Oral Health. doi: 10.1186/s12903-026-09735-z. Full text in Research Archive Show summary

  Background Oral findings are common among older adults, but it is unclear whether they vary with the duration of antiresorptive therapy (ART) exposure or relate to the severity of osteoporosis in postmenopausal women. Methods In this cross-sectional cohort ( n  = 129), postmenopausal women undergoing osteoporosis assessment/follow-up were stratified by ART exposure duration: no current ART control (G1, n  = 50), short ART (G2, 3–5 years; n  = 39), and long ART (G3, > 5 years; n  = 40). The prespecified primary oral endpoint was any mucosal finding ( oral_mucosal_any ), defined as ≥ 1 prespecified mucosal lesion category at oral examination. The oral_mucosal_any endpoint was analysed by component to distinguish traumatic from non-traumatic mucosal findings. Secondary oral endpoints included tooth and molar counts, periodontal findings, and the number of mucosal lesion categories. Group differences were analysed using age- and BMI-adjusted regression (G1 reference). Secondary analyses compared oral findings across fracture-burden strata and hip BMD/T-score categories and evaluated whether oral variables improved discrimination for hip osteoporosis (total hip T-score ≤ − 2.5) beyond age, BMI, and ART group. Results Mucosal findings were common and non-monotonic across ART groups (G1: 52.0%, G2: 30.8%, G3: 52.5%). Among the 59 participants with any mucosal finding, traumatic changes were present in 43 (72.9%); in a mutually exclusive classification, 38 (64.4%) had traumatic-only findings. In age- and BMI-adjusted models, short ART was associated with lower odds of oral_mucosal_any versus controls (OR 0.38, 95% CI 0.16–0.93; p  = 0.035), whereas long ART did not differ (OR 0.94, 95% CI 0.38–2.33; p  = 0.894). Tooth and molar counts, periodontal burden, and non-traumatic mucosal findings showed no robust graded pattern with ART duration. Oral findings were broadly similar across fracture-burden strata and hip BMD categories. Adding total teeth and oral_mucosal_any increased apparent Area Under the Curve (AUC) for hip osteoporosis from 0.795 to 0.820, but optimism-corrected AUC changed only from 0.736 to 0.741 (corrected ΔAUC = 0.005). Conclusions In this cross-sectional cohort, common oral findings did not show a robust graded duration–response pattern across ART exposure groups and were not consistently associated with fracture burden or hip BMD strata. The broad mucosal endpoint was largely driven by common traumatic findings and should be interpreted as a clinically pragmatic but biologically heterogeneous endpoint. Oral variables added negligible optimism-corrected discrimination beyond age, BMI, and ART group.

• Hlinková, Jana; Huo, Yiru; Sukul, Mousumi; Lewis, David J.; Reseland, Janne Elin & Haugen, Håvard Jostein [Show all 8 contributors for this article] (2026). Dual-crosslinked chitosan nanofibres - Balancing mechanical enhancement with cytotoxic risk. Biomaterials Advances. ISSN 2772-9516. p. 215050–215050. doi: 10.1016/j.bioadv.2026.215050. Full text in Research Archive Show summary

  This study evaluated the effects of dual-crosslinking strategies on the mechanical performance and biocompati- bility of chitosan-norbornene (Chi-NB) nanofibres for tissue reconstruction. Chi-NB, bearing 28.6 ± 1.4 mol% alkene groups, was processed into nanofibres via solution blow spinning. Dual crosslinking was conducted by photo-initiated thiol-ene crosslinking with dithiothreitol (DTT), achieving >95% norbornene conversion with minimal thiol oxidation, followed by exposure to tannic acid (TA). Structural and chemical validation was per- formed using SEM, NMR, XPS, FT-IR, and tensile testing. In vitro, unmodified fibres supported robust cell viabil- ity, however, TA/DTT-modified fibres caused up to 15-fold higher LDH release at low seeding-densities, mirrored in indirect conditioned medium exposure, implicating cytotoxic leachates. Confocal imaging confirmed cell ad- hesion and cytoskeletal organisation whereas transcript analysis revealed altered expression of genes related to stress response, metabolism, growth, and differentiation. Overall, TA/DTT crosslinking improved nanofibre me- chanical properties but introduced bioactive residues, highlighting the need for post-processing and seeding den- sity optimisation. These findings support the translational potential of Chi-NB scaffolds in skin and neural tissue engineering, but future refinements are required for these applications.

• Småland-Reksten, Agnes; Agger, Anne Eriksson; Lian, Aina-Mari; Reseland, Janne Elin & Krüger, Tormod Bjartveit (2026). Bisphosphonate and statin: adverse effects of co-medication on wound healing in in vitro models of periodontal tissues. Acta Odontologica Scandinavica. ISSN 0001-6357. 85, p. 125–133. doi: 10.2340/aos.v85.45585. Full text in Research Archive
• Agger, Anne Eriksson; Hlinkova, Jana; Reseland, Janne Elin & Samara, Athina (2026). 3D models for oral inflammation using gingival fibroblasts, lipopolysaccharides and hypoxia | Scientific Reports. Scientific Reports. doi: 10.1038/s41598-026-47648-7. Full text in Research Archive Show summary

  Three-dimensional (3D) in vitro models that more faithfully recapitulate human tissue architecture are essential to advance mechanistic insight into inflammatory diseases. We developed and characterized a 3D human gingival fibroblast spheroid-system to dissect the combined effects of hypoxia and inflammation, two central features of host–pathogen interactions in periodontal disease and other chronic inflammatory conditions. Using controlled oxygen environments and stimulation with E. coli lipopolysaccharide (LPS) and IL-1β, we show that hypoxia alone markedly alters spheroid morphology, producing smaller aggregates with thinner rims, while the combination of hypoxia and inflammation yields the most prominent structural disruption. Cross-section analyses reveal condition-dependent remodeling of extracellular matrix and cytoskeletal organization, with coordinated reductions in fibronectin, collagen I/III, integrin β1, and filamentous actin. Gene expression profiling confirms suppression of extracellular matrix (ECM)-related and adhesion genes under hypoxia and combined stress, whereas secretome analysis demonstrates robust upregulation of pro-inflammatory cytokines and chemokines (IL-6, IL-8, MCP-1, TNFα) and angiogenic VEGFα. Despite these marked structural and immunological shifts, cell viability remained largely preserved. This 3D system captures key features of fibroblast responses to inflammatory and hypoxic cues, providing a human-relevant platform for studies of tissue remodeling, cytokine signaling, and microenvironmental stress relevant to host–pathogen–driven disease.

• Yang, Yang; Pullisaar, Helen; Reseland, Janne Elin & Ma, Jingzhi (2025). Molecular insights into irisin’s role in the regulation of programmed cell death: mechanisms and therapeutic potential. Journal of Molecular Medicine. ISSN 0946-2716. 104(1). doi: 10.1007/s00109-025-02623-z. Full text in Research Archive
• Hlinkova, Jana; Dziemidowicz, Karolina; Ullrich, Mathilde M.; Agger, Anne Eriksson; Lian, Aina-Mari & Reseland, Janne Elin [Show all 7 contributors for this article] (2025). Neural growth patterns: how random and aligned fibers guide 3D cell organization and pseudospheroid formation. Frontiers in Bioengineering and Biotechnology. 13. doi: 10.3389/fbioe.2025.1659965. Full text in Research Archive Show summary

  Background and purpose Electrospun biomaterials replicate the structural complexity of the extracellular matrix (ECM), providing mechanical support and promoting neural cell survival and organization. Fiber orientation is a key determinant of neural cell behavior, influencing adhesion, migration, and differentiation. This study investigates how high seeding density combined with fiber directionality shapes SH-SY5Y culture morphology, gene expression, and early network formation; all critical factors for the design of next-generation scaffolds for neural tissue engineering. Methods Polycaprolactone (PCL) scaffolds with either random or aligned fiber orientation were fabricated via monoaxial electrospinning. Human SH-SY5Y neuroblastoma cells were seeded at high density and cultured for 7 days, and cell viability was assessed by lactate dehydrogenase (LDH) activity. Neural, ECM, and differentiation markers were analyzed using quantitative PCR, Luminex cytokine profiling, and confocal immunofluorescence. Results Hydrophobic PCL fibers supported cell adhesion, migration, and proliferation when cells were seeded in small clusters. After 7 days, cell coverage of the fiber-mat was significantly higher on random fibers compared to aligned ones (27.7% vs. 15.8%). Fiber orientation influenced both culture morphology and gene expression. Pseudospheroids formed on both substrates, that differed in perimeter (348.5 µm on random vs. 450.5 µm on aligned fibers, p &lt; 0.05), with no significant difference in thickness (38.4 ± 7.7 µm vs. 43.2 ± 5.5 µm). mRNA expression of connexin 43 and β3-tubulin increased significantly from day 1 to day 7 on random fibers. On aligned fibers, mRNA patterns resembled cells cultured on glass (control), with elevated connexin 31 and doublecortin over time. Immunofluorescence showed early enrichment of nestin on aligned fibers (day 1), and greater expression of β3-tubulin, acetylated tubulin, and connexin 31 on aligned substrates, whereas fibronectin 1 was more prominent on random fibers. Conclusion Fiber orientation significantly affected SH-SY5Y cell behaviour, including adhesion, formation of pseudospheroids, and differentiation marker expression under high-density conditions. Random and aligned fibers elicited distinct structural patterns and molecular responses, highlighting the importance of scaffold architecture in the rational design of neuroregenerative platforms. To our knowledge, this is the first study to describe scaffold-anchored neural pseudospheroids as a distinct model from conventional suspension spheroids.

• Munir, Arooj; Agger, Anne Eriksson; Samara, Athina; Reseland, Janne Elin & Solberg, Lene Bergendal (2025). Enhancing human osteoblast to osteocyte-like cell differentiation using 25-hydroxyvitamin D3 and all-trans retinoic acid combination. European Cells and Materials. p. 145–157. doi: 10.22203/eCM.v051a09. Full text in Research Archive Show summary

  Background: The individual effects of the 25-hydroxyvitamin D3 (25(OH)D3) and all-trans retinoic acid (ATRA) on osteogenesis have been studied in two-dimensional (2D) in vitro models, but the combined effect of these vitamins remains largely unexplored. Therefore, to address this knowledge gap we evaluated the effect of different concentrations of 25(OH)D3 and ATRA, individually and in combination, on differentiation of primary human osteoblasts (hOBs) over a 21-day period. Methods: The growth of hOBs, alkaline phosphatase (ALP) activity (cell bound and secreted), and the expression of bone-related markers were comprehensively evaluated at both gene expression level using real-time polymerase chain reaction (RT-PCR) and the proteins secretion through multiplex immunoassays. Results: Both 25(OH)D3 and ATRA enhanced hOBs differentiation. However, the combination of 10−6 M 25(OH)D3 and 10−5 M ATRA demonstrated the most pronounced effect, characterized by reduction in cell growth and enhancement in differentiation. This was further validated by elevated relative expression of osteoblast and osteocyte markers at both mRNA level (collagen type I alpha 1 (COL1A1), podoplanin (E11), and dentin matrix acidic phosphoprotein 1 (DMP1), and at protein level (osteopontin (OPN), osteocalcin (OCN), sclerostin (SOST), and fibroblast growth factor 23 (FGF23)). Additionally, 25(OH)D3 and ATRA were found to regulate the expression of key receptors involved in osteoblasts differentiation, including retinoic acid receptor alpha (RARα), retinoid X receptor beta (RXRβ), and vitamin D receptor (VDR). Conclusions: This study demonstrates that a combination of 10−6 M 25(OH)D3 and 10−5 M ATRA effectively enhanced the differentiation of hOBs to osteocyte-like cells in vitro.

• Tien, Nguyen D.; Geng, Tianxiang; Coelho, David José Caetano; Reseland, Janne Elin; Lyngstadaas, Ståle Petter & Blaker, Jonathan James [Show all 7 contributors for this article] (2025). Multilayer gradient chitosan fiber scaffolds for skin tissue regeneration with enhanced mechanical strength and cellular infiltration. Reactive & functional polymers. ISSN 1381-5148. 214. doi: 10.1016/j.reactfunctpolym.2025.106276. Full text in Research Archive Show summary

  Using the solution blow spinning technique, a trilayer structure scaffold was developed for skin tissue engineering. The scaffold, composed of chitosan/polyethylene oxide (CHI/PEO) fibers, mimicking the skin's natural structure, featuring a fiber diameter gradient ranging from 300 to 1200 nm and controlled porosity. Neutralization with potassium carbonate solution stabilized the chitosan-based fibers and enhanced their mechanical properties. The subsequent removal of PEO during neutralization created a porosity gradient (80–50%) across the scaffold layers, resulting in interconnected pores essential for cell infiltration and nutrient transport. The neutralized scaffolds enhanced mechanical performance with an ultimate tensile strength of 29.4 ± 4.8 MPa and Young’s modulus of 6.5 ± 1.1 MPa. The toughness was found to be 2.3 ± 1.0 MJ/m³. The gradient design closely mimics aspects of the skin's extracellular matrix. It substantially enhances the scaffold’s mechanical integrity—doubling tensile strength, Young’s modulus, and toughness compared to the as-spun structure—while preserving the essential flexibility required for dynamic wound environments. In vitro evaluations using co-cultures of normal human dermal fibroblasts (NHDF) and human epidermal keratinocytes (HEKa) demonstrated suitable cell viability, adhesion, and proliferation on the scaffold. Moreover, confocal imaging confirmed HEKa cellular infiltration throughout the more porous scaffold parts and dense NHDF layers on the less porous fiber layer, effectively mimicking the spatial organization of native skin layers. Our results underscore the significant potential of this gradient chitosan fiber scaffold as a scalable and versatile platform for skin tissue engineering. This innovative scaffold offers a promising new strategy for accelerating wound healing and achieving durable tissue regeneration by seamlessly integrating superior mechanical performance with enhanced cellular dynamics.

• Reppe, Sjur; Reseland, Janne Elin; Prijatelj,, Vid; Prediger, Michael; Nogueira, Liebert Parreiras & Utheim, Tor Paaske [Show all 9 contributors for this article] (2024). The DLEU2–miR-15a–16-1 Cluster Is a Determinant of Bone Microarchitecture and Strength in Postmenopausal Women and Mice. International Journal of Molecular Sciences. ISSN 1661-6596. 25(23), p. 12724–12724. doi: 10.3390/ijms252312724. Full text in Research Archive Show summary

  This study explores how select microRNAs (miRNAs) influence bone structure in humans and in transgenic mice. In trabecular bone biopsies from 84 postmenopausal women (healthy, osteopenic, and osteoporotic), we demonstrate that DLEU2 (deleted in lymphocytic leukemia 2)-encoded miR-15a-5p is strongly positively associated with bone mineral density (BMD) at different skeletal sites. In bone transcriptome analyses, miR-15a-5p levels correlated positively with the osteocyte characteristic transcripts SOST (encoding sclerostin) and MEPE (Matrix Extracellular Phosphoglycoprotein), while the related miR-15b-5p showed a negative association with BMD and osteoblast markers. The data imply that these miRNAs have opposite roles in bone remodeling with distinct actions on bone cells. Expression quantitative trait loci (eQTL) variants confirmed earlier DLEU2 associations. Furthermore, a novel variant (rs12585295) showed high localization with transcriptionally active chromatin states in osteoblast primary cell cultures. The supposition that DLEU2-encoded miRNAs have an important regulatory role in bone remodeling was further confirmed in a transgenic mice model showing that miR-15a/16-1-deleted mice had significantly higher percentage bone volume and trabecular number than the wild type, possibly due to prenatal actions. However, the three-point mechanical break force test of mice femurs showed a positive correlation between strength and miR-15a-5p/miR-16-5p levels, indicating differential effects on cortical and trabecular bone. Moreover, these miRNAs appear to have distinct and complex actions in mice prenatally and in adult humans, impacting BMD and microstructure by regulating bone cell transcription. However, detailed interactions between these miRNAs and their downstream mechanisms in health and disease need further clarification.

• Agger, Anne Eriksson; Samara, Athina; Geng, Tianxiang; Olstad, Ole Kristoffer & Reseland, Janne Elin (2024). Mimicking and in vitro validating chronic inflammation in human gingival fibroblasts. Archives of Oral Biology. ISSN 0003-9969. 169, p. 1–11. doi: 10.1016/j.archoralbio.2024.106113. Full text in Research Archive Show summary

  Objective The aim of this study was to identify and validate in vitro conditions that may mimic the translational, cytokine and chemokine profiles observed in human inflamed gingiva in vivo. Design Primary human gingiva fibroblast cells (HFIB-G) were cultured under serum starvation conditions (0 – 10 %), supplemented with increasing lipopolysaccharide (LPS) concentrations (0.1, 1, or 10 µg/ml) from two bacterial strains E. coli and P. gingivalis and 0.1, 1, or 10 ng/ml recombinant interleukin 1β (IL-1β), alone or in combinations. The levels of cytokines/chemokines were measured in the cell culture medium by Luminex, and gene expression was quantified by Affymetrix microarrays at 24, 48 and 72 h. Results Inflammation markers were not elevated after stimulation with P. gingivalis LPS, while E. coli LPS and IL-1β individually increased the secretion of interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) to the cell culture medium. IL-1β administration also increased the secretion of several factors, including tumor necrosis factor (TNFα). However, the combination of 1 µg/ml E. coli LPS, 1 ng/ml IL-1β and serum starvation led to increased secretion of IL-6, TNFα, in addition to other factors found in inflamed tissue. Gene expression analyses revealed that this combination not only enhanced the expression interleukins/chemokines genes but also T helper cell signaling and matrix metalloproteinases. Conclusion Serum reduction in cell culture medium together with the administration of E. coli LPS and IL-1β resulted in gene expression and secreted cytokine/chemokine profiles similar to that found in vivo during chronic inflammation.

• Vogelaar, Thomas Daniel; Agger, Anne Eriksson; Reseland, Janne Elin; Linke, Dirk; Jenssen, Håvard & Lund, Reidar (2024). Crafting Stable Antibiotic Nanoparticles via Complex Coacervation of Colistin with Block Copolymers. Biomacromolecules. ISSN 1525-7797. 25(7), p. 4267–4280. doi: 10.1021/acs.biomac.4c00337. Full text in Research Archive Show summary

  To combat the ever-growing increase of multidrug-resistant (MDR) bacteria, action must be taken in the development of antibiotic formulations. Colistin, an effective antibiotic, was found to be nephrotoxic and neurotoxic, consequently leading to a ban on its use in the 1980s. A decade later, colistin use was revived and nowadays used as a last-resort treatment against Gram-negative bacterial infections, although highly regulated. If cytotoxicity issues can be resolved, colistin could be an effective option to combat MDR bacteria. Herein, we investigate the complexation of colistin with poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA) block copolymers to form complex coacervate core micelles (C3Ms) to ultimately improve colistin use in therapeutics while maintaining its effectiveness. We show that well-defined and stable micelles can be formed in which the cationic colistin and anionic PMAA form the core while PEO forms a protecting shell. The resulting C3Ms are in a kinetically arrested and stable state, yet they can be made reproducibly using an appropriate experimental protocol. By characterization through dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS), we found that the best C3M formulation, based on long-term stability and complexation efficiency, is at charge-matching conditions. This nanoparticle formulation was compared to noncomplexed colistin on its antimicrobial properties, enzymatic degradation, serum protein binding, and cytotoxicity. The studies indicate that the antimicrobial properties and cytotoxicity of the colistin-C3Ms were maintained while protein binding was limited, and enzymatic degradation decreased after complexation. Since colistin-C3Ms were found to have an equal effectivity but with increased cargo protection, such nanoparticles are promising components for the antibiotic formulation toolbox.

• Printzell, Lisa; Reseland, Janne Elin; Edin, Nina Frederike Jeppesen; Ellingsen, Jan Eirik & Tiainen, Hanna (2023). Backscatter from therapeutic doses of ionizing irradiation does not impair cell migration on titanium implants in vitro. Clinical Oral Investigations. ISSN 1432-6981. doi: 10.1007/s00784-023-05128-6. Full text in Research Archive Show summary

  Objective The influence of radiation backscatter from titanium on DNA damage and migration capacity of human osteoblasts (OBs) and mesenchymal stem cells (MSCs) may be critical for the osseointegration of dental implants placed prior to radiotherapy. In order to evaluate effects of radiation backscatter, the immediate DNA damage and migration capacity of OBs and MSCs cultured on titanium or plastic were compared after exposure to ionizing irradiation. Materials and methods Human OBs and MSCs were seeded on machined titanium, moderately rough fluoride-modified titanium, or tissue culture polystyrene, and irradiated with nominal doses of 2, 6, 10, or 14 Gy. Comet assay was performed immediately after irradiation, while a scratch wound healing assay was initiated 24 h post-irradiation. Fluorescent live cell imaging documented the migration. Results DNA damage increased with higher dose and with backscatter from titanium, and MSCs were significantly more affected than OBs. All doses of radiation accelerated the cell migration on plastic, while only the highest dose of 10 Gy inhibited the migration of both cell types on titanium. Conclusions High doses (10 Gy) of radiation inhibited the migration capacity of both cell types on titanium, whereas lower doses (2 and 6 Gy) did not affect the migration of either OBs or MSCs. Clinical relevance Fractionated doses of 2 Gy/day, as distributed in conventional radiotherapy, appear not to cause severe DNA damage or disturb the migration of OBs or MSCs during osseointegration of dental implants.

• Gamage, Thilini Hansamali Gamage Yaddehi; Grabmayr, Herwig; Horvath, Ferdinand; Fahrner, Marc; Misceo, Doriana & Louch, William Edward [Show all 21 contributors for this article] (2023). A single amino acid deletion in the ER Ca2+ sensor STIM1 reverses the in vitro and in vivo effects of the Stormorken syndrome-causing R304W mutation. Science Signaling. ISSN 1945-0877. 16(771). doi: 10.1126/scisignal.add0509. Full text in Research Archive
• Geng, Tianxiang; Zheng, Mengxue; Wang, Yongfeng; Reseland, Janne Elin & Samara, Athina (2023). An artificial intelligence prediction model based on extracellular matrix proteins for the prognostic prediction and immunotherapeutic evaluation of ovarian serous adenocarcinoma. Frontiers in Molecular Biosciences. 10. doi: 10.3389/fmolb.2023.1200354. Full text in Research Archive Show summary

  Background: Ovarian Serous Adenocarcinoma is a malignant tumor originating from epithelial cells and one of the most common causes of death from gynecological cancers. The objective of this study was to develop a prediction model based on extracellular matrix proteins, using artificial intelligence techniques. The model aimed to aid healthcare professionals to predict the overall survival of patients with ovarian cancer (OC) and determine the efficacy of immunotherapy. Methods: The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) data collection was used as the study dataset, whereas the TCGA-Pancancer dataset was used for validation. The prognostic importance of 1068 known extracellular matrix proteins for OC were determined by the Random Forest algorithm and the Lasso algorithm establishing the ECM risk score. Based on the gene expression data, the differences in mRNA abundance, tumour mutation burden (TMB) and tumour microenvironment (TME) between the high- and low-risk groups were assessed. Results: Combining multiple artificial intelligence algorithms we were able to identify 15 key extracellular matrix genes, namely, AMBN, CXCL11, PI3, CSPG5, TGFBI, TLL1, HMCN2, ESM1, IL12A, MMP17, CLEC5A, FREM2, ANGPTL4, PRSS1, FGF23 , and confirm the validity of this ECM risk score for overall survival prediction. Several other parameters were identified as independent prognostic factors for OC by multivariate COX analysis. The analysis showed that thyroglobulin (TG) targeted immunotherapy was more effective in the high ECM risk score group, while the low ECM risk score group was more sensitive to the RYR2 gene-related immunotherapy. Additionally, the patients with low ECM risk scores had higher immune checkpoint gene expression and immunophenoscore levels and responded better to immunotherapy. Conclusion: The ECM risk score is an accurate tool to assess the patient’s sensitivity to immunotherapy and forecast OC prognosis.

• Spoutil, Frantisek; Aranaz-Novaliches, Goretti; Prochazkova, Michaela; Wald, Tomas; Novosadova, Vendula & Kasparek, Petr [Show all 14 contributors for this article] (2023). Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions. Scientific Reports. 13(1). doi: 10.1038/s41598-023-28388-4. Full text in Research Archive Show summary

  Highly specialized enamel matrix proteins (EMPs) are predominantly expressed in odontogenic tissues and diverged from common ancestral gene. They are crucial for the maturation of enamel and its extreme complexity in multiple independent lineages. However, divergence of EMPs occured already before the true enamel evolved and their conservancy in toothless species suggests that non-canonical functions are still under natural selection. To elucidate this hypothesis, we carried out an unbiased, comprehensive phenotyping and employed data from the International Mouse Phenotyping Consortium to show functional pleiotropy of amelogenin, ameloblastin, amelotin, and enamelin, genes, i.e. in sensory function, skeletal morphology, cardiovascular function, metabolism, immune system screen, behavior, reproduction, and respiratory function. Mice in all KO mutant lines, i.e. amelogenin KO, ameloblastin KO, amelotin KO, and enamelin KO, as well as mice from the lineage with monomeric form of ameloblastin were affected in multiple physiological systems. Evolutionary conserved motifs and functional pleiotropy support the hypothesis of role of EMPs as general physiological regulators. These findings illustrate how their non-canonical function can still effect the fitness of modern species by an example of influence of amelogenin and ameloblastin on the bone physiology.

• Agger, Anne Eriksson; Reseland, Janne Elin; Hjelkrem, Erik; Lian, Aina-Mari; Hals, Else Kristine Breivik & Zandi, Homan [Show all 7 contributors for this article] (2023). Are comorbidities associated with the cytokine/chemokine profile of persistent apical periodontitis? Clinical Oral Investigations. ISSN 1432-6981. 27, p. 5203–5215. doi: 10.1007/s00784-023-05139-3. Full text in Research Archive
• Yang, Yang; Geng, Tianxiang; Samara, Athina; Olstad, Ole Kristoffer; He, Jianying & Agger, Anne Eriksson [Show all 11 contributors for this article] (2023). Recombinant irisin enhances the extracellular matrix formation, remodeling potential, and differentiation of human periodontal ligament cells cultured in 3D. Journal of Periodontal Research. ISSN 0022-3484. 58(2), p. 336–349. doi: 10.1111/jre.13094. Full text in Research Archive Show summary

  Abstract Background Irisin is expressed in human periodontal ligament (hPDL), and its administration enhances growth, migration and matrix deposition in hPDL cells cultured in monolayers in vitro. Objectives To identify whether irisin affects the gene expression patterns directing the morphology, mechanical properties, extracellular matrix (ECM) formation, osteogenic activity and angiogenic potential in hPDL cell spheroids cultured in 3D. Materials and Methods Spheroids of primary human hPDL cells were generated in a rotational 3D culture system and treated with or without irisin. The gene expression patterns were evaluated by Affymetrix microarrays. The morphology of the spheroids was characterized using histological staining. Mechanical properties were quantified by nanoindentation. The osteogenic and angiogenic potential of spheroids were assessed through immunofluorescence staining for collagen type I, periostin fibronectin and von Willebrand factor (vWF), and mRNA expression of osteogenic markers. The secretion of multiple myokines was evaluated using Luminex immunoassays. Results Approximately 1000 genes were differentially expressed between control and irisin-treated groups by Affymetrix. Several genes related to ECM organization were differentially expressed, and multiple deubiquitinating enzymes were upregulated in the irisin-exposed samples analyzed. These represent cellular and molecular mechanisms indicative of a role for irisin in tissue remodeling. Irisin induced a rim-like structure on the outer region of the hPDL spheroids, ECM-related protein expression and the stiffness of the spheroids were enhanced by irisin. The expression of osteogenic and angiogenetic markers was increased by irisin. Conclusions Irisin altered the morphology in primary hPDL cell-derived spheroids, enhanced its ECM deposition, mechanical properties, differentiation and remodeling potential.

• Yang, Yang; Pullisaar, Helen; Stunes, Astrid Kamilla; Nogueira, Liebert Parreiras; Syversen, Unni & Reseland, Janne Elin (2023). Irisin reduces orthodontic tooth movement in rats by promoting the osteogenic potential in the periodontal ligament. European Journal of Orthodontics. ISSN 0141-5387. 45(6), p. 842–853. doi: 10.1093/ejo/cjad021. Full text in Research Archive Show summary

  Objectives Positive effects of irisin on osteogenic differentiation of periodontal ligament (PDL) cells have been identified previously, this study aims to examine its effect on orthodontic tooth movement (OTM) in vivo. Materials and methods The maxillary right first molars of male Wistar rats (n = 21) were moved mesially for 14 days, with submucosal injection of two dosages of irisin (0.1 or 1 μg) or phosphate-buffered saline (control) every third day. OTM was recorded by feeler gauge and micro-computed tomography (μCT). Alveolar bone and root volume were analysed using μCT, and plasma irisin levels by ELISA. Histological characteristics of PDL tissues were examined, and the expression of collagen type I, periostin, osteocalcin (OCN), von Willebrand factor (vWF) and fibronectin type III domain-containing protein 5 (FNDC5) in PDL was evaluated by immunofluorescence staining. Results Repeated 1 μg irisin injections suppressed OTM on days 6, 9, and 12. No significant differences were observed in OTM in the 0.1 μg irisin group, or in bone morphometric parameters, root volume or plasma irisin, compared to control. Resorption lacunae and hyalinization were found at the PDL-bone interface on the compression side in the control, whereas they were scarce after irisin administration. The expression of collagen type I, periostin, OCN, vWF, and FNDC5 in PDL was enhanced by irisin administration. Limitations The feeler gauge method may overestimate OTM. Conclusions Submucosal irisin injection reduced OTM by enhancing osteogenic potential of PDL, and this effect was more significant on the compression side.

• Reseland, Janne Elin; Heyward, Catherine Anne & Samara, Athina (2023). Revisiting ameloblastin; addressing the EMT-ECM axis above and beyond oral biology. Frontiers in Cell and Developmental Biology. 11. doi: 10.3389/fcell.2023.1251540. Full text in Research Archive Show summary

  Ameloblastin (AMBN) is best characterized for its role in dental enamel formation, regulating cell differentiation and mineralization, and cell matrix adhesion. However, AMBN has also been detected in mesenchymal stem cells in addition to bone, blood, and adipose tissue. Using immunofluorescence in a pilot scheme, we identified that AMBN is expressed in different parts of the gastrointestinal (GI) tract. AMBN mRNA and protein detection in several tissues along the length of the GI tract suggests a role for AMBN in the structure and tissue integrity of the extracellular matrix (ECM). Intracellular AMBN expression in subsets of cells indicates a potential alternative role in signaling processes. Of note, our previous functional AMBN promoter analyses had shown that it contains epithelial–mesenchymal transition (EMT) regulatory elements. ΑΜΒΝ is herein presented as a paradigm shift of the possible associations and the spatiotemporal regulation of the ECM regulating the EMT and vice versa, using the example of AMBN expression beyond oral biology.

• Munir, Arooj; Reseland, Janne Elin; Tiainen, Hanna; Haugen, Håvard Jostein; Sikorski, Pawel & Christiansen, Emil [Show all 9 contributors for this article] (2023). Osteocyte-Like Cells Differentiated From Primary Osteoblasts in an Artificial Human Bone Tissue Model. JBMR Plus. p. 1–10. doi: 10.1002/jbm4.10792. Full text in Research Archive Show summary

  In vitro models of primary human osteocytes embedded in natural mineralized matrix without artificial scaffolds are lacking. We have established cell culture conditions that favored the natural 3D orientation of the bone cells and stimulated the cascade of signaling needed for primary human osteoblasts to differentiate into osteocytes with the characteristically phenotypical dendritic network between cells. Primary human osteoblasts cultured in a 3D rotating bioreactor and incubated with a combination of vitamins A, C, and D for up to 21 days produced osteospheres resembling native bone. Osteocyte-like cells were identified as entrapped, stellate-shaped cells interconnected through canaliculi embedded in a structured, mineralized, collagen matrix. These cells expressed late osteoblast and osteocyte markers such as osteocalcin (OCN), podoplanin (E11), dentin matrix acidic phosphoprotein 1 (DMP1), and sclerostin (SOST). Organized collagen fibrils, observed associated with the cell hydroxyapatite (HAp) crystals, were found throughout the spheroid and in between the collagen fibrils. In addition to osteocyte-like cells, the spheroids consisted of osteoblasts at various differentiation stages surrounded by a rim of cells resembling lining cells. This resemblance to native bone indicates a model system with potential for studying osteocyte-like cell differentiation, cross-talk between bone cells, and the mineralization process in a bonelike structure in vitro without artificial scaffolds. In addition, natural extracellular matrix may allow for the study of tissue-specific biochemical, biophysical, and mechanical properties.

• Ulmner, Mattias; Sugars, Rachael; Naimi-Akbar, Aron; Reseland, Janne Elin & Lund, Bodil (2023). General joint hypermobility in temporomandibular joint disease; clinical characteristics, biomarkers, and surgical aspects. Heliyon. 9(12). doi: 10.1016/j.heliyon.2023.e23051. Full text in Research Archive Show summary

  Objectives: This study aimed at identifying biomarkers in the temporomandibular joint (TMJ) synovial tissue analysing 28 extra cellular matrix proteins in TMJ diseased patients, classified with either general joint hypermobility (GJH) or normal joint mobility (NJM), and to compile clinical and protein characterisation to reveal potential surgical predictive factors. Study design: A prospective observational cohort study including 97 consecutive patients scheduled for TMJ surgery was performed. Joint mobility and several other predefined clinical varivables were recorded. Synovial tissue was harvested during surgery followed by examination using multi-analytic profiling. A multivariate quantile regression model was used for analysis purposes. Results: The GJH/NJM ratio was 2:5. The GJH cohort were younger (P = 0.001) and more likely to be women (P = 0.026) compared to the NJM cohort. None of the protein concentrations could be correlated to joint mobility in the multivariate regression model, but often to the variable TMJ diagnosis. The surgical outcome after the six-month follow-up were equal between GJH and NJM patients. Conclusions: GJH was more common in the study cohort compared to general population frequencies, but GJH was not a negative factor for surgical outcome. Young age and female gender correlated to GJH. No TMJ biomarkers were GJH specific, and the results suggested that TMJ diagnosis more strongly correlated to the protein profile compared to GJH and the other investigated variables.

• Printzell, Lisa; Reseland, Janne Elin; Edin, Nina Frederike Jeppesen; Tiainen, Hanna & Ellingsen, Jan Eirik (2023). The dose-dependent impact of γ-radiation reinforced with backscatter from titanium on primary human osteoblasts. Biomaterial Investigations in Dentistry. 10(1). doi: 10.1080/26415275.2023.2209116. Full text in Research Archive Show summary

  In head and neck cancer patients receiving dental implants prior to radiotherapy, backscatter from titanium increases the radiation dose close to the surface, and may affect the osseointegration. The dose-dependent effects of ionizing radiation on human osteoblasts (hOBs) were investigated. The hOBs were seeded on machined titanium, moderately rough fluoride-modified titanium, and tissue culture polystyrene, and cultured in growth- or osteoblastic differentiation medium (DM). The hOBs were exposed to ionizing γ-irradiation in single doses of 2, 6 or 10 Gy. Twenty-one days post-irradiation, cell nuclei and collagen production were quantified. Cytotoxicity and indicators of differentiation were measured and compared to unirradiated controls. Radiation with backscatter from titanium significantly reduced the number of hOBs but increased the alkaline phosphatase activity in both types of medium when adjusted to the relative cell number on day 21. Irradiated hOBs on the TiF-surface produced similar amounts of collagen as unirradiated controls when cultured in DM. The majority of osteogenic biomarkers significantly increased on day 21 when the hOBs had been exposed to 10 Gy, while the opposite or no effect was observed after lower doses. High doses reinforced with backscatter from titanium resulted in smaller but seemingly more differentiated subpopulations of osteoblasts.

• Pietryga, Krzysztof; Reczyńska-Kolman, Katarzyna; Reseland, Janne Elin; Haugen, Håvard Jostein; Larreta-Garde, Véronique & Pamula, Elzbieta (2023). Biphasic monolithic osteochondral scaffolds obtained by diffusion-limited enzymatic mineralization of gellan gum hydrogel. Biocybernetics and Biomedical Engineering (BBE). ISSN 0208-5216. doi: 10.1016/j.bbe.2022.12.009. Full text in Research Archive Show summary

  Biphasic monolithic materials for the treatment of osteochondral defects were produced from polysaccharide hydrogel, gellan gum (GG). GG was enzymatically mineralized by alkaline phosphatase (ALP) in the presence of calcium glycerophosphate (CaGP). The desired distribution of the calcium phosphate (CaP) mineral phase was achieved by limiting the availability of CaGP to specific parts of the GG sample. Therefore, mineralization of GG was facilitated by the diffusion of CaGP, causing the formation of the CaP gradient. The distribution of CaP was analyzed along the cross section of the GG. The formation of a CaP gradient was mainly affected by the mineralization time and the ALP concentration. The formation of CaP was confirmed by Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy and mapping, as well as energy-dispersive X-ray spectroscopy (EDX) mapping of the interphase. The microstructure of mineralized and non-mineralized parts of the material was characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM) showing sub-micrometer CaP crystal formation, resulting in increased surface roughness. Compression tests and rheometric analyzes showed a 10-fold increase in stiffness of GG mineralized part. Concomitantly, micromechanical tests performed by AFM showed an increase of Young's modulus from 17.8 to more than 200 kPa. In vitro evaluation of biphasic scaffolds was performed in contact with osteoblast-like MG-63 cells. The mineralized parts of GG were preferentially colonized by the cells over the non-mineralized parts. The results showed that osteochondral scaffolds of the desired structure and properties can be made from GG using a diffusion-limited enzymatic mineralization method.

• Mosti, Mats Peder; Stafne, Signe; Sujan, Md Abu Jafar; Redalen, Kathrine Røe; Marthinsen, Anne Beate Langeland & Skallerud, Bjørn Helge [Show all 12 contributors for this article] (2022). Strength training reduces radiation-induced bone deterioration and maintains lean mass in a rat model. Bone Reports. 16, p. 101369–101369. doi: 10.1016/j.bonr.2022.101369. Full text in Research Archive
• Reseland, Janne Elin & Yang, Yang (2022). Expression and Regulation of FNDC5/irisin in Periodontium and Dental Pulp. Archives of Dentistry. ISSN 2689-6222. doi: 10.33696/dentistry.4.022. Full text in Research Archive
• Krüger, Tormod Bjartveit; Syversen, Unni; Herlofson, Bente Brokstad; Lian, Aina-Mari & Reseland, Janne Elin (2022). Targeting a therapeutically relevant concentration of alendronate for in vitro studies on osteoblasts. Acta Odontologica Scandinavica. ISSN 0001-6357. 80(8), p. 619–625. doi: 10.1080/00016357.2022.2072522. Full text in Research Archive Show summary

  Objective Bisphosphonates like alendronate mainly exert their effects on osteoclasts. However, osteoblasts are also affected, but exposed to a much lower concentration in vivo than the osteoclasts. Given that the effects are dose-dependent, the intention of the study was to identify a therapeutically relevant concentration of alendronate for in vitro studies on osteoblasts. Materials and methods Primary human osteoblasts were incubated with alendronate (5, 20 and 100 µM) for 1, 3, 7 and 14 days. Proliferation and viability were assessed, and the effects on cellular growth and function were evaluated by multianalyte profiling of selected proteins in cell culture media using the Luminex 200TM. Results The viability was not affected by any of the dosages. Exposure to 5 µM alendronate had a neutral effect on osteoblast proliferation, and on secretion of osteogenic and inflammatory markers, while enhancing synthesis of a marker of angiogenesis. 20 µM alendronate induced a decline in proliferation and affected angiogenic and osteogenic biomarkers adversely. 100 µM alendronate reduced proliferation dramatically, and this dosage was excluded from further experiments. Conclusion A concentration of 5 µM alendronate exerted effects on human osteoblasts that may translate to those observed in vivo and could therefore be relevant for in vitro studies.

• Hongji, Yan; Deus, Gustavo De; Kristoffersen, Ida Marie; Wiig, Elisabeth; Reseland, Janne Elin & Johnsen, Gaute Floer [Show all 8 contributors for this article] (2022). Regenerative Endodontics by Cell Homing: A Review of Recent Clinical trials. Journal of Endodontics. ISSN 0099-2399. 49(1), p. 4–17. doi: 10.1016/j.joen.2022.09.008. Full text in Research Archive Show summary

  The conventional treatment for irreversibly inflamed or necrotic teeth is root canal treatment or apexification. As an alternative approach, regenerative endodontics aims to regenerate the damaged ‘‘pulp-like’’ tissue, which can preserve the teeth’ vitality and sensitivity while avoiding necrosis, offering solutions to overcome the limitations of conventional treatments. The main clinical benefit is root maturation. The ‘‘pulp-like’’ tissue does not refer to regenerated pulp tissue with an odontoblastic layer or the formation of pulp-dentin complexes. The cell homing technique is built on endogenous stem cells and their capacity to regenerate tissue. Its Regenerative Endodontic Procedures success criteria are defined by the American Association of Endodontists (AAE). The purpose of this article is to provide an overview of vital pulp tissue and various strategies to promote regeneration of damaged pulp tissue. The cell homing technique will be reviewed through clinical trials. Cell homing refers to the migration or infiltration of endogenous cells into the cite when stimulated by physiochemical or biological stimuli or by passive flow with a blood clot from the apical tissue. The local microenvironment is critical for the settlement, proliferation, and differentiation of the infiltrated cells to regenerate the damaged pulp tissue. Current possibilities and the limits of today’s cell homing therapy will be discussed.

• Schröder, Maria Elisabeth; Reseland, Janne Elin & Haugen, Håvard Jostein (2022). Osteoblasts in a Perfusion Flow Bioreactor—Tissue Engineered Constructs of TiO2 Scaffolds and Cells for Improved Clinical Performance. Cells. 11(13), p. 1995–1995. doi: 10.3390/cells11131995. Full text in Research Archive Show summary

  Combining biomaterial scaffolds with cells serves as a promising strategy for engineering critical size defects; however, homogenous cellular growth within large scaffolds is challenging. Mechanical stimuli can enhance bone regeneration by modulating cellular growth and differentiation. Here, we compare dynamic seeding in a perfusion flow bioreactor with static seeding for a synthetic bone scaffold for up to 21 days using the cell line MC3T3-E1 and primary human osteoblast, confocal laser scanning microscopy, and real-time reverse transcriptase-polymerase chain reaction. The secretion of bone-related proteins was quantified using multiplex immunoassays. Dynamic culture improved cellular distribution through the TiO2 scaffold and induced a five-fold increase in cell number after 21 days. The relative mRNA expression of osteopontin of MC3T3-E1 was 40-fold enhanced after 7 and 21 days at a flow rate of 0.08 mL/min, and that of collagen type I alpha I expression was 18-fold after 21 days. A flow rate of 0.16 mL/min was 10-fold less effective. Dynamic culture increased the levels of dickkopf-related protein 1 (60-fold), osteoprotegrin (29-fold), interleukin-6 (23-fold), interleukin-8 (36-fold), monocyte chemoattractant protein 1 (28-fold) and vascular endothelial growth factor (6-fold) in the medium of primary human osteoblasts after 21 days compared to static seeding. The proposed method may have clinical potential for bone tissue engineering.

• Ribeiro, João P.; Domingues, Rui M.A.; Babo, Pedro S.; Nogueira, Liebert Parreiras; Reseland, Janne Elin & Reis, Rui L. [Show all 8 contributors for this article] (2022). Highly elastic and bioactive bone biomimetic scaffolds based on platelet lysate and biomineralized cellulose nanocrystals. Carbohydrate Polymers. ISSN 0144-8617. 292. doi: 10.1016/j.carbpol.2022.119638. Full text in Research Archive
• Süslü, Safiyye; Høgestøl, Ingvild Kristine; Lian, Aina-Mari; Eriksen, Erik Fink & Reseland, Janne Elin (2022). Osteotropic proteins in bone marrow do not reflect abundance in bone and bone remodeling in obese females. Obesity Medicine. ISSN 2451-8476. 32, p. 1–8. doi: 10.1016/j.obmed.2022.100408. Full text in Research Archive
• Tien, Nguyen D.; Geng, Tianxiang; Heyward, Catherine Anne; Reseland, Janne Elin; Lyngstadaas, Ståle Petter & Blaker, Jonathan James [Show all 7 contributors for this article] (2022). Solution blow spinning of highly deacetylated chitosan nanofiber scaffolds for dermal wound healing. Materials Science and Engineering C: Materials for Biological Applications. ISSN 0928-4931. 137. doi: 10.1016/j.bioadv.2022.212871. Full text in Research Archive Show summary

  Biocompatible fibrous scaffolds based on highly deacetylated chitosan were fabricated using high-throughput solution blow spinning. Scanning electron microscopy analysis revealed that the chitosan nanofiber scaffolds had ultrafine and continuous fibers (300–1200 nm) with highly interconnected porous structures (30–75% porosity), mimicking some aspects of the native extracellular matrix in skin tissue. Post-treatment of as-spun nanofibers with aqueous potassium carbonate solution resulted in a fibrous scaffold with a high chitosan content that retained its fibrous structural integrity for cell culture. Analysis of the mechanical properties of the chitosan nanofiber scaffolds in both dry and wet conditions showed that their strength and durability were sufficient for wound dressing applications. Significantly, the wet scaffold underwent remarkable elastic deformation during stretch such that the elongation at break dramatically increased to up to 44% of its original length, showing wavy fiber morphology near the break site. The culture of normal human dermal fibroblast cells onto scaffolds for 1–14 days demonstrated that the scaffolds were highly compatible and a suitable platform for cell adhesion, viability, and proliferation. Secretion profiles of wound healing-related proteins to the cell culture medium demonstrated that chitosan fibers were a promising scaffold for wound healing applications. Overall, the dense fibrous network with high porosity of the chitosan nanofiber scaffold and their mechanical properties indicate that they could be used to design and fabricate new materials that mimic the epidermis layer of natural skin.

• Geng, Tianxiang; Heyward, Catherine Anne; Chen, Xi; Zheng, Mengxue; Yang, Yang & Reseland, Janne Elin (2022). Comprehensive Analysis Identifies Ameloblastin-Related Competitive Endogenous RNA as a Prognostic Biomarker for Testicular Germ Cell Tumour. Cancers. 14(8). doi: 10.3390/cancers14081870. Full text in Research Archive
• Arnason, Niels Arni; Johannsson, Freyr; Landrö, Ragna; Hardarsson, Björn; Gudmundsson, Sveinn & Lian, Aina-Mari [Show all 9 contributors for this article] (2022). Protein Concentrations in Stored Pooled Platelet Concentrates Treated with Pathogen Inactivation by Amotosalen Plus Ultraviolet a Illumination. Pathogens. ISSN 2076-0817. 11(3). doi: 10.3390/pathogens11030350. Full text in Research Archive
• Sukul, Mousumi; Sahariah, Priyanka; Lauzon, Hélène L.; Borges, João; Másson, Már & Mano, Joao F. [Show all 8 contributors for this article] (2021). In vitro biological response of human osteoblasts in 3D chitosan sponges with controlled degree of deacetylation and molecular weight. Carbohydrate Polymers. ISSN 0144-8617. 254, p. 117434–117434. doi: 10.1016/j.carbpol.2020.117434. Full text in Research Archive Show summary

  We have studied the effect of chitosan sponges, produced from chitosan batches with distinct degree of deacetylation (DDA) and molecular weight (Mw), on the adhesion, growth and differentiation of primary human osteoblasts with an aim to offer a suitable tool for guided bone regeneration. All the chitosan sponges revealed similar microstructure, irrespective of the DDA (58, 73, 82, 88, and 91 %) and Mw (749, 547, 263, 215, and 170 kDa, respectively). Cell spreading was higher on sponges having a higher DDA. Higher DDA induced a more pronounced increase in alkaline phosphatase activity, osteopontin (OPN), vascular endothelial growth factor-A (VEGF), interleukin-6 (IL-6), and reduction in monocyte chemoattractant protein-1 (MCP-1), sclerostin (SOST) and dickkopf related protein-1 as compared to lower DDA. Lower DDA induced the increased secretion of osteoprotegerin and SOST as compared to higher DDA. The combination of higher DDA and Mw induced an increased secretion of VEGF and IL-6, however reduced the secretion of OPN as compared to chitosan with similar DDA but with lower Mw. In summary, the variations in cellular responses to the different chitosan sponges indicate a potential for individual tailoring of desired responses in guided

• Syversen, Unni; Mosti, Mats Peder; Mynarek, Ida Maria; Vedal, Trude Seselie Jahr; Aasarød, Kristin Matre & Basso, Trude [Show all 11 contributors for this article] (2021). Evidence of impaired bone quality in men with type 1 diabetes: A cross-sectional study. Endocrine Connections. 10(8), p. 955–964. doi: 10.1530/EC-21-0193. Full text in Research Archive Show summary

  Objective Type 1 diabetes (T1D) is associated with substantial fracture risk. Bone mineral density (BMD) is, however, only modestly reduced, suggesting impaired bone microarchitecture and/or bone material properties. Yet, the skeletal abnormalities have not been uncovered. Men with T1D seem to experience a more pronounced bone loss than their female counterparts. Hence, we aimed to examine different aspects of bone quality in men with T1D. Design and Methods In this cross-sectional study, men with T1D and healthy male controls were enrolled. BMD (femoral neck, total hip, lumbar spine, whole body) and spine trabecular bone score (TBS) were measured by dual x-ray absorptiometry, and bone material strength index (BMSi) was measured by in vivo impact microindentation. HbA1c and bone turnover markers were analyzed. Results Altogether, 33 men with T1D (43 ± 12 years) and 28 healthy male controls (42 ± 12 years) were included. Subjects with T1D exhibited lower whole-body BMD than controls (P = 0.04). TBS and BMSi were attenuated in men with T1D vs controls (P = 0.016 and P = 0.004, respectively), and T1D subjects also had a lower bone turnover. The bone parameters did not differ between subjects with or without diabetic complications. Duration of disease correlated negatively with femoral neck BMD but not with TBS or BMSi. Conclusions This study revealed compromised bone material strength and microarchitecture in men with T1D. Moreover, our data confirm previous studies which found a modest decrease in BMD and low bone turnover in subjects with T1D. Accordingly, bone should be recognized as a target of diabetic complications.

• Kruger, Tormod Bjartveit; Herlofson, Bente Brokstad; Lian, Aina-Mari; Syversen, Unni & Reseland, Janne Elin (2021). Alendronate and omeprazole in combination reduce angiogenic and growth signals from osteoblasts. Bone Reports. 14:100750, p. 1–7. doi: 10.1016/j.bonr.2021.100750. Full text in Research Archive Show summary

  Objective: Due to gastrointestinal side effects of oral bisphosphonates (BPs), proton pump inhibitors (PPIs) are often prescribed. PPIs may enhance the risk of osteonecrosis of the jaw, a rare side effect of BPs. Therefore, the objective of this study was to evaluate the effects of the oral BP alendronate (ALN) and the PPI omeprazole (OME) alone and in combination on primary human osteoblasts and gingival fibroblasts in vitro. Methods: Human gingival fibroblasts and normal human osteoblasts were incubated with either 5 μM of ALN or 1 μM of OME, or ALN + OME for 1, 3, 7 or 14 days. Effect on viability was evaluated by the lactate dehydrogenase activity in the medium and on proliferation by quantifying 3H-thymidin incorporation. Multianalyte profiling of proteins in cell culture media was performed using the Luminex 200TM system to assess the effect on selected bone markers and cytokines. Results: The proliferation of osteoblasts and fibroblasts was reduced upon exposure to ALN + OME. ALN induced an early, temporary rise in markers of inflammation, and OME and ALN + OME promoted a transient decline. An initial increase in IL-13 occurred after exposure to all three options, whereas ALN + OME promoted IL-8 release after 7 days. OME and ALN + OME promoted a transient reduction in vascular endothelial growth factor (VEGF) from osteoblasts, whereas ALN and ALN + OME induced a late rise in VEGF from fibroblasts. Osteoprotegerin release was enhanced by ALN and suppressed by OME and ALN + OME. Conclusions: ALN + OME seemed to exaggerate the negative effects of each drug alone on human osteoblasts and gingival fibroblasts. The anti-proliferative effects, modulation of inflammation and impairment of angiogenesis, may induce unfavorable conditions in periodontal tissue facilitating development of osteonecrosis.

• Zhu, Hao; Haugen, Håvard Jostein; Perale, Giuseppe; Reseland, Janne Elin; Nogueira, Liebert Parreiras & Cantalapiedra, Antonio gonzalez [Show all 11 contributors for this article] (2021). Tailoring Resorption Rates and Osteogenic Response in Xeno-Hybrid Bone Grafts: The Effect of Added Gelatins. Engineering (Beijing). ISSN 2095-8099. 13, p. 197–208. doi: 10.1016/j.eng.2021.01.010. Full text in Research Archive Show summary

  Bone defects resulting from trauma, surgery, congenital malformations, and other factors are among the most common health problems nowadays. Although current strategies such as autografts and allografts are recognized as the most successful treatments for stimulating bone regeneration, limitations such as graft source and complications still exist. SmartBone® is a xeno-hybrid bone graft (made from bovine bone matrix, poly(L-lactic-co-ε-caprolactone), and gelatin) with a positive clinical record for bone regeneration. In this study, the formulation for designing xeno-hybrid bone grafts using gelatins from different sources (bovine- and porcine-derived gelatin, with bone grafts named SBN and SPK, respectively) was investigated, and the biological responses were evaluated in vitro and in vivo. The results demonstrate that gelatins from both bovine and porcine sources can be loaded onto SmartBone® successfully and safely, withstanding the aggressive manufacturing processes. Different bone cell responses were observed in vitro. SBN was found to enhance osteocalcin secretion while SPK was found to upregulate osteopontin from human osteoblasts. In vivo, both bone grafts promoted osteogenesis, but SPK degraded earlier than SBN. Our findings suggest that SBN and SPK provide different yet comparable solutions for optimizing the bone resorption and regeneration balance. These xeno-hybrid bone grafts possess ideal potential for bone defect repairing.

• Yang, Yang; Pullisaar, Helen; Landin, Maria Augusta Dos S Silva; Heyward, Catherine Anne; Schröder, Maria & Geng, Tianxiang [Show all 8 contributors for this article] (2021). FNDC5/irisin is expressed and regulated differently in human periodontal ligament cells, dental pulp stem cells and osteoblasts. Archives of Oral Biology. ISSN 0003-9969. doi: 10.1016/j.archoralbio.2021.105061. Full text in Research Archive Show summary

  Objective To examine the expression and regulation of fibronectin type III domain-containing protein 5/irisin (FNDC5/irisin) in primary human periodontal ligament (hPDL) cells, dental pulp stem cells (hDPCs) and osteoblasts (hOBs). Methods FNDC5/irisin was identified in sections of paraffin embedded rat maxillae, cryo-sections of 3D cultured spheroids hPDL cells, hDPCs and hOBs, 2D cultured hPDL cells, hDPCs and hOBs by immunohistochemistry. The expression of FNDC5/irisin was identified by qPCR, followed by sequencing of the qPCR product. Regulation of FNDC5/irisin expression in hPDL cells, hDPCs and hOBs were evaluated after administration of different concentrations of irisin and all-trans retinoic acid (ATRA). qPCR and ELISA were used to identify expression and secretion of FNDC5/irisin in odontoblast-like differentiation of hDPCs. Results FNDC5/irisin was confirmed to be present in rat periodontium and dental pulp regions, as well as in 2D and 3D cultured hPDL cells, hDPCs and hOBs. BLAST analyses verified the generated nucleotide alignments matched human FNDC5/irisin. FNDC5/irisin gene expression was enhanced during odontoblast-like differentiation of hDPCs whereas the secretion of the protein was decreased compared to control. The protein signals in rat periodontal and pulpal tissues were higher than that of alveolar bone, and the expression of FNDC5/irisin was differently regulated by recombinant irisin and ATRA in hPDL cells and hDPCs compared to hOBs. Conclusions FNDC5/irisin expression was verified in rodent periodontium and dental pulp, and in hPDL cells, hDPCs and hOBs. The FNDC5/irisin expression was regulated by recombinant irisin and ATRA. Finally, expression and secretion of FNDC5/irisin were affected during odontoblast-like differentiation of hDPCs.

• Brunetti, Giacomina; Storlino, Giuseppina; Oranger, Angela; Colaianni, Graziana; Faienza, Maria F & Ingravallo, Giuseppe [Show all 14 contributors for this article] (2020). LIGHT/TNFSF14 regulates estrogen deficiency‐induced bone loss. Journal of Pathology. ISSN 0022-3417. 250, p. 440–451. doi: 10.1002/path.5385. Full text in Research Archive
• Ulmner, Mattias; Sugars, Rachael; Naimi-Akbar, Aron; Suslu, Safiyye; Reseland, Janne Elin & Kruger-Weiner, Carina [Show all 7 contributors for this article] (2020). Synovial tissue cytokine profile in disc displacement of the temporomandibular joint. Journal of Oral Rehabilitation. ISSN 0305-182X. 47(10), p. 1202–1211. doi: 10.1111/joor.13051. Full text in Research Archive Show summary

  Background Symptomatic disc displacement (DD) of the temporomandibular joint (TMJ) may cause pain and limited mouth opening. The aetiopathogenesis is obscure and probably complex, which makes the diagnostic classification crude and mainly based on clinical criteria rather than disease mechanisms, and tissue characteristics. Objectives The study aim was to characterise and quantify synovial tissue in DD, where specific cytokine patterns might serve as potential biomarkers. Methods An observational cohort study was performed harvesting synovial tissue from 63 patients: 44 with DD without reduction (DDwoR) and 19 with DD with reduction (DDwR). DDwoR was subdivided depending on type of onset (sudden, n = 17; delayed, n = 27), and DDwR served as the control group. Proteins were extracted from tissue samples and investigated in a multi‐analytic profiling system. Results DDwoR patients had significantly higher concentrations in 12 out of 28 analysed cytokines compared to DDwR. In the same statistical model, significantly lower concentrations of interferon gamma‐induced protein (IP) 10, osteoprotegerin (OPG) and RANTES were detected in DDwoR patients. Women showed significantly higher concentrations of epidermal growth factor and interleukin (IL) 1ra compared to men. DDwoR with sudden onset had significant higher concentrations of bone morphogenetic protein 4, eotaxin and IL‐8 compared to DDwoR with delayed onset. Conclusions Characterising the biomarker panel for TMJ conditions may serve as suggestible targets for disease classification and novel treatment options. The significantly lower concentrations of IP‐10, OPG and RANTES could be proposed as putative markers for the separation of the studied conditions to other TMJ diseases.

• Schröder, Maria; Riksen, Elisabeth Aurstad; He, Jianying; Skallerud, Bjørn Helge; Møller, Mona Elisabeth & Lian, Aina-Mari [Show all 8 contributors for this article] (2020). Vitamin K2 modulates vitamin D induced mechanical properties of human 3D bone spheroids in vitro. JBMR Plus. 4(9). doi: 10.1002/jbm4.10394. Full text in Research Archive Show summary

  Rotational culture promotes primary human osteoblasts (hOBs) to form three-dimensional (3D) multicellular spheroids with bone tissue-like structure without any scaffolding material. Cell-based bone models enable us to investigate the effect of different agents on the mechanical strength of bone. Given that low dietary intake of both vitamin D and K is negatively associated with fracture risk, we aimed to assess the effect of these vitamins in this system. Osteospheres of hOBs were generated with menaquinone-4 (MK-4; 10μM) and 25-hydroxyvitamin D3 [25(OH)D3; 0.01μM], alone and in combination, or without vitamins. The mechanical properties were tested by nanoindentation using a flat-punch compression method, and the mineralized extracellular bone matrix was characterized by microscopy. The in vitro response of hOBs to MK-4 and 25(OH)D3 was further evaluated in two-dimensional (2D) cultures and in the 3D bone constructs applying gene expression analysis and multiplex immunoassays. Mechanical testing revealed that 25(OH)D3 induced a stiffer and MK-4 a softer or more flexible osteosphere compared with control. Combined vitamin conditions induced the same flexibility as MK-4 alone. Enhanced levels of periostin (p < 0.001) and altered distribution of collagen type I (COL-1) were found in osteospheres supplemented with MK-4. In contrast, 25(OH)D3 reduced COL-1, both at the mRNA and protein levels, increased alkaline phosphatase, and stimulated mineral deposition in the osteospheres. With the two vitamins in combination, enhanced gene expression of periostin and COL-1 was seen, as well as extended osteoid formation into the central region and increased mineral deposition all over the area. Moreover, we observed enhanced levels of osteocalcin in 2D and osteopontin in 3D cultures exposed to 25(OH)D3 alone and combined with MK-4. In conclusion, the two vitamins seem to affect bone mechanical properties differently: vitamin D enhancing stiffness and K2 conveying flexibility to bone. These effects may translate to increased fracture resistance in vivo. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

• Rahmati, Maryam; Silva, Eduardo A.; Reseland, Janne Elin; Heyward, Catherine Anne & Haugen, Håvard Jostein (2020). Biological responses to physicochemical properties of biomaterial surface. Chemical Society Reviews. ISSN 0306-0012. 49(15), p. 5178–5224. doi: 10.1039/d0cs00103a. Full text in Research Archive Show summary

  Biomedical scientists use chemistry-driven processes found in nature as an inspiration to design biomaterials as promising diagnostic tools, therapeutic solutions, or tissue substitutes. While substantial consideration is devoted to the design and validation of biomaterials, the nature of their interactions with the surrounding biological microenvironment is commonly neglected. This gap of knowledge could be owing to our poor understanding of biochemical signaling pathways, lack of reliable techniques for designing biomaterials with optimal physicochemical properties, and/or poor stability of biomaterial properties after implantation. The success of host responses to biomaterials, known as biocompatibility, depends on chemical principles as the root of both cell signaling pathways in the body and how the biomaterial surface is designed. Most of the current review papers have discussed chemical engineering and biological principles of designing biomaterials as separate topics, which has resulted in neglecting the main role of chemistry in this field. In this review, we discuss biocompatibility in the context of chemistry, what it is and how to assess it, while describing contributions from both biochemical cues and biomaterials as well as the means of harmonizing them. We address both biochemical signal-transduction pathways and engineering principles of designing a biomaterial with an emphasis on its surface physicochemistry. As we aim to show the role of chemistry in the crosstalk between the surface physicochemical properties and body responses, we concisely highlight the main biochemical signal-transduction pathways involved in the biocompatibility complex. Finally, we discuss the progress and challenges associated with the current strategies used for improving the chemical and physical interactions between cells and biomaterial surface.

• Rahmati, Maryam; Frank, Matthias Johannes; Walter, Martin Sebastian; Cabrer, Marta Monjo; Satué, María & Reseland, Janne Elin [Show all 8 contributors for this article] (2020). Osteoimmunomodulatory effects of enamel matrix derivate and strontium coating layers: A short- and long-term in vivo study. ACS Applied Bio Materials (AABM). 3, p. 5169–5181. doi: 10.1021/acsabm.0c00608. Full text in Research Archive Show summary

  Over the past few years, surface modification of implant surface has gained substantial attention as a promising solution to avoid the failure of biomaterials after implantation. Although researchers suggest several strategies for surface functionalization of titanium based implants, only few studies have compared the osteoimmunomodulatory effects of ionic nanostructure and biofunctionalization in the same biological model. Enamel matrix derivate (EMD) and strontium are both known for their positive influences on bone cell responses. In this study, we functionalized the titanium-zirconium implant surface with EMD and strontium using an electrochemical cathodic polarization method. Afterwards, we evaluated the osteoimmunomodulatory effects of EMD or strontium coated titanium zirconium implants in the tibia of eight Grey Bastard Chinchillas rabbits. We performed 2&3D micro-CT, wound fluid, histologic, and histomorphometric analyses on bone tissues after 4- and 8-weeks implantation. Although the results could indicate some differences between groups regarding the bone quality, there was no difference in bone amount or volume. EMD stimulated higher ALP activity and lower cytotoxicity in wound fluid, as well as a lower expression of inflammatory markers after 8 weeks indicating its osteoimmunomodulatory effects after implantation. Overall, the results suggested that ionic nanostructure modification and biofunctionalization might be useful in regulating the immune responses to implants.

• Sukul, Mousumi; Cama, Giuseppe; Dubruel, Peter; Reseland, Janne Elin & Haugen, Håvard Jostein (2020). Methacrylation increase growth and differentiation of primary human osteoblasts for gelatin hydrogels. Emergent Materials. ISSN 2522-5731. 3, p. 559–566. doi: 10.1007/s42247-020-00101-5. Full text in Research Archive Show summary

  The role of gelatin methacrylate hydrogels with varying degree of methacrylation (69% and 84%) was accessed with FTIR, NMR, microCT and subsequently exposure to human osteoblasts. The cells responded positively to the degree of methacrylation and showed attachment, growth and proliferated on both hydrogels. The cell reacted differently to the degree of methacrylation with higher proliferation on higher substitution; however, cell differentiation behavior was improved for less substitution. The secretion of late osteogenic markers (Osteoprotegerin (OPG), Osteopontin (OPN) and Osteocalcein (OCN)) and angiogenic factor Vascular endothelial growth factor (VEGF) was increased for gelatin methacrylate hydrogels with 69% degree of methacrylation and thus would be the better candidate for future bone regenerative applications amongst the three tested hydrogels

• Pham, Thi Ngoc Maria Huong; Haugen, Håvard Jostein & Reseland, Janne Elin (2020). Fluoride Modification of Titanium Surfaces Enhance Complement Activation. Materials. 13(3), p. 684–684. doi: 10.3390/ma13030684. Full text in Research Archive Show summary

  Immediately after dental implant insertion, blood will be in direct contact and interact with the implant surface and activates inflammatory responses and complement cascades within seconds. The aim of the present study was to determine the ability of fluoride-modified titanium surfaces to activate complement cascades using the human buffy coat as model. The buffy coats were exposed to hydrofluoric acid-modified surfaces for a short time and its responses were compared to controls. Identification and quantification of complement cascade biomarkers were conducted using ELISA kits and multianalyte profiling using Luminex. A lower level of C3 at 30 min and increased levels of C4, MIP-4, CRP, and pigment epithelium-derived factor at 360 min were found on modified surfaces as compared to controls. We found no significant differences in the levels of C3a, C5a, C Factor H, α2M, ApoA1, ApoC3, ApoE, Prealbumin, α1AT, and SAP in modified surfaces in the buffy coats. We conclude that titanium surfaces treated with hydrofluoric acid modify the levels of specific biomarkers related to the complement cascade and angiogenesis and, thus, tissue growth, remodeling and repair, as this may play a role in the enhanced clinical performance of fluoride-modified Ti dental implants.

• Øyri, Hauk Furnes; Jensen, Janicke Liaaen; Barkvoll, Pål; Jonsdottir, Olga Hrønn; Reseland, Janne Elin & Bjørnland, Tore (2020). Incidence of alveolar osteitis after mandibular third molar surgery. Can inflammatory cytokines be identified locally? Acta Odontologica Scandinavica. ISSN 0001-6357. 79(3), p. 205–211. doi: 10.1080/00016357.2020.1817546. Full text in Research Archive Show summary

  Objectives The aims of the present study were to evaluate the relative incidence of alveolar osteitis (AO) after mandibular third molar surgery, post-operative findings and local expression of bone markers and cytokines. Study design In 445 patients, unilateral surgical third molars extractions were undertaken (584 teeth). Bone markers and cytokines were explored at the AO side and on the un-operated contralateral side and compared with the levels in samples from a control group of 18 persons without AO. Results The relative incidence of AO was 4.6%. Patients (n = 27) with AO were invited to participate in the study and 21 (77.8%) did so. Patients with AO had 1–4 extra visits for treatment of AO, the mean follow-up time was 2.6 days for all patients. There were significantly higher levels of bone markers and cytokines in the AO site compared with the un-operated contralateral site, except for Epidermal growth factor (EGF). No significant difference in expression of bone markers and cytokines between the AO and control groups was found. Lower maximum inter-incisor opening (MIO) was correlated with increased Macrophage inflammatory protein 1 alpha. A negative correlation between patients’ complaint of trismus and MIO was seen. Conclusions The relative incidence of AO was low in our patient group treated with surgical removal of third molars. AO was more frequently seen in female patients. Treatment of AO required up to four extra visits. The study provides some information on the role of cytokines in AO; but further studies are required.

• Haugen, Håvard Jostein; Marovic, Danijela; Par, Matej; Thieu, Minh Khai Le; Reseland, Janne Elin & Johnsen, Gaute Floer (2020). Bulk Fill Composites Have Similar Performance to Conventional Dental Composites. International Journal of Molecular Sciences. ISSN 1661-6596. 21(15), p. 5136–5136. doi: 10.3390/ijms21145136. Full text in Research Archive Show summary

  The aim of the study was to perform comprehensive characterization of two commonly used bulk fill composite materials (SDR Flow (SDR) and Filtek™ Bulk Fill Flowable Restorative (FBF) and one conventional composite material (Tetric EvoCeram; TEC). Eleven parameters were examined: flexural strength (FS), flexural modulus (FM), degree of conversion, depth of cure, polymerisation shrinkage (PS), filler particle morphology, filler mass fraction, Vickers hardness, surface roughness following simulated toothbrush abrasion, monomer elution, and cytotoxic reaction of human gingival fibroblasts, osteoblasts, and cancer cells. The degree of conversion and depth of cure were the highest for SDR, followed by FBF and TEC, but there was no difference in PS between them. FS was higher for bulk fill materials, while their FM and hardness were lower than those of TEC. Surface roughness decreased in the order TEC→SDR→FBF. Bisphenol A-glycidyl methacrylate (BisGMA) and urethane dimethacrylate were found in TEC and FBF eluates, while SDR released BisGMA and triethylene glycol dimethacrylate. Conditioned media accumulated for 24h from FBF and TEC were cytotoxic to primary human osteoblasts. Compared to the conventional composite, the tested bulk fill materials performed equally or better in most of the tests, except for their hardness, elastic modulus, and biocompatibility with osteoblasts.

• Maal, Mehrnaz Beheshti; Ellingsen, Stig Aanerød; Reseland, Janne Elin & Verket, Anders (2020). Experimental implantoplasty outcomes correlate with fibroblast growth in vitro. BMC Oral Health. 20, p. 25–25. doi: 10.1186/s12903-020-1012-1. Full text in Research Archive Show summary

  Background Implantoplasty is an option in peri-implantitis treatment, but little is known about the effect on the soft tissue. The aim of the study was to characterize surface roughness following experimental implantoplasty and to examine its effect on human fibroblast growth and secretion of selected proteins. Methods Titanium grade IV coins were mechanically treated with six different rotating bur sequences; diamond burs or carbide burs alone, or followed by either Arkansas stone bur or silicone burs. Machined and rough-surface sandblasted, acid-etched (SLA) coins were used as control. The surface topography was characterized by scanning electron microscope and profilometer. Human gingival fibroblasts from two donors were cultured on the coins to quantify the effect on cell morphology, growth, and protein secretion by confocal microscopy and multiplex immunoassay. Results All surface roughness parameters were lower for the surfaces treated with experimental implantoplasty than for the SLA surface, and the sequence of carbide burs followed by silicone burs rendered the least rough surface of the test groups. The implantoplasty procedures changed the elemental composition of the titanium surface. High surface roughness showed a weak to moderate negative correlation to fibroblast growth, but induced a higher secretion of VEGF, IL-6 and MCP-3 to the cell medium compared to the least rough surfaces of the test groups. At day 30 fibronectin levels were higher in the SLA group. Conclusions The surface roughness following implantoplasty demonstrated a weak to moderate negative correlation with the growth of fibroblasts. The addition of Arkansas stone and silicon burs to the experimental implantoplasty bur protocol rendered an initial increase in fibroblast growth. Implantoplasty altered the elemental composition of the titanium surface, and had an effect on the fibroblast cytokine secretion and fibronectin levels.

• Haugen, Håvard Jostein; Basu, Poulami; Sukul, Mousumi; Mano, Joao F. & Reseland, Janne Elin (2020). Injectable biomaterials for Dental Tissue Regeneration. International Journal of Molecular Sciences. ISSN 1661-6596. 21, p. 3442–3442. doi: 10.3390/ijms21103442. Full text in Research Archive Show summary

  Injectable biomaterials scaffolds play a pivotal role for dental tissue regeneration, as such materials are more applicable in the dental field, particularly when compared to pre-formed scaffolds. The defects in maxilla-oral area are normally small, confined and sometimes hard to access. This narrative review described different types of biomaterials for dental tissue regeneration, also discussing the potential use of nanofibres for dental tissues. Various studies suggest that the tissue engineering approaches involving the use of injectable biomaterials have the potential of restoring not only dental tissue function but also their biological purposes

• Chahal, Aman S; Schweikle, Manuel; Lian, Aina-Mari; Reseland, Janne Elin; Haugen, Håvard Jostein & Tiainen, Hanna (2020). Osteogenic potential of poly(ethylene glycol)-amorphous calcium phosphate composites on human mesenchymal stem cells. Journal of Tissue Engineering. 11. doi: 10.1177/2041731420926840. Full text in Research Archive Show summary

  Synthetic hydrogel-amorphous calcium phosphate composites are promising candidates to substitute biologically sourced scaffolds for bone repair. While the hydrogel matrix serves as a template for stem cell colonisation, amorphous calcium phosphate s provide mechanical integrity with the potential to stimulate osteogenic differentiation. Here, we utilise composites of poly(ethylene glycol)-based hydrogels and differently stabilised amorphous calcium phosphate to investigate potential effects on attachment and osteogenic differentiation of human mesenchymal stem cells. We found that functionalisation with integrin binding motifs in the form of RGD tripeptide was necessary to allow adhesion of large numbers of cells in spread morphology. Slow dissolution of amorphous calcium phosphate mineral in the scaffolds over at least 21 days was observed, resulting in the release of calcium and zinc ions into the cell culture medium. While we qualitatively observed an increasingly mineralised extracellular matrix along with calcium deposition in the presence of amorphous calcium phosphate-loaded scaffolds, we did not observe significant changes in the expression of selected osteogenic markers.

• Vetyskova, Veronika; Zouharova, Monika; Bednarova, Lucie; Vaněk, Ondřej; Sázelová, Petra & Kašička, Václav [Show all 14 contributors for this article] (2020). Characterization of AMBN I and II isoforms and study of their Ca2+ binding properties. International Journal of Molecular Sciences. ISSN 1661-6596. 21, p. 9293–9293. doi: 10.3390/ijms21239293. Full text in Research Archive Show summary

  Ameloblastin (Ambn) as an intrinsically disordered protein (IDP) stands for an important role in the formation of enamel—the hardest biomineralized tissue commonly formed in vertebrates. The human ameloblastin (AMBN) is expressed in two isoforms: full-length isoform I (AMBN ISO I) and isoform II (AMBN ISO II), which is about 15 amino acid residues shorter than AMBN ISO I. The significant feature of AMBN—its oligomerization ability—is enabled due to a specific sequence encoded by exon 5 present at the N-terminal part in both known isoforms. In this study, we characterized AMBN ISO I and AMBN ISO II by biochemical and biophysical methods to determine their common features and differences. We confirmed that both AMBN ISO I and AMBN ISO II form oligomers in in vitro conditions. Due to an important role of AMBN in biomineralization, we further addressed the calcium (Ca2+)-binding properties of AMBN ISO I and ISO II. The binding properties of AMBN to Ca2+ may explain the role of AMBN in biomineralization and more generally in Ca2+ homeostasis processes.

• Shabestari, Maziar; Shabestari, Yashar Ghadakchi; Landin, Maria Augusta Dos S Silva; Pepaj, Milaim; Cleland, Timothy & Reseland, Janne Elin [Show all 7 contributors for this article] (2020). Altered protein levels in bone marrow lesions of hip osteoarthritis: Analysis by proteomics and multiplex immunoassays. International Journal of Rheumatic Diseases. ISSN 1756-1841. 23(6), p. 788–799. doi: 10.1111/1756-185X.13843. Full text in Research Archive Show summary

  Aim To assess tissue level changes of proteome and cytokine profiles of subchondral bone in hip osteoarthritis (OA) affected by bone marrow lesions (BMLs). We compared significant protein level differences in osteoarthritic bone with BMLs to control bone without bone marrow lesions. Methods Subchondral bone biopsies were taken from femoral heads of end‐stage osteoarthritis patients with (BML, n = 21) and without (CON, n = 9) BMLs. Proteins were extracted through a standardized Trizol protocol and used in the subsequent analyses. Angiogenesis and bone markers were assessed using multiplex immunoassays (Luminex). Liquid chromatography tandem mass spectrometry (LC‐MS/MS) was performed to detect significant differences in proteome and peptide profiles between BML and CON. Results Multiplex immunoassays revealed increased tissue contents of vascular endothelial growth factors (VEGF‐A/C/D), endothelin‐1, angiopoietin‐2 and interleukin‐6 (IL‐6) in bone with BMLs compared to control bone, whereas osteoprotegerin levels were reduced. Mass spectrometry demonstrated pronounced increase in the levels of hemoglobin (73‐fold), serum albumin (30‐fold), alpha‐1‐antitrypsin (9‐fold), apolipoprotein A1 (4.7‐fold), pre‐laminin‐A/C (3.7‐fold) and collagen‐alpha1‐XII (3‐fold) in BMLs, while aggrecan core protein (ACAN) and hyaluronan and proteoglycan link protein 1 (HAPL1) decreased 37‐ and 29‐fold respectively. Conclusion Reduced osteoprotegerin, ACAN and HAPL1 are consistent with osteoclastic activation and high remodeling activity in BMLs. The pronounced increase in angiogenesis markers, hemoglobin and serum albumin support the presence of increased vascularity in subchondral bone affected by BMLs in OA. VEGFs and IL‐6 are known nociceptive modulators, and increased levels are in keeping with pain being a clinical feature frequently associated with BMLs.

• Rahmati, Maryam; Lyngstadaas, Ståle Petter; Reseland, Janne Elin; Andersbakken, Ingrid; Haugland, Heidi Straume & López-peña, Mónica [Show all 9 contributors for this article] (2020). Coating doxycycline on titanium-based implants: two in vivo studies. Bioactive Materials. 5(4), p. 787–797. doi: 10.1016/j.bioactmat.2020.05.007. Full text in Research Archive Show summary

  Regardless of the substantial progress in designing titanium-based dental implants and aseptic techniques, infection remains as the most common complication after implantation surgeries. Although, having a weakened immune system or systematic diseases is not seen as contraindicated for dental implants anymore, controlling the immune system is required to avoid surgical site infections after implantation. These patients have to control the surgical site infections by taking a high daily dose of oral antibiotics after dental implantation. The antibiotics oral administration has many side effects such as gastrointestinal symptoms, skin rashes and thrush. Coating antibiotics on the biomaterials surface could be a promising solution to reduce these disadvantages through locally releasing antibiotics in a controlled manner. The aim of this study was to investigate the effects of doxycycline coating layer on titanium-zirconium alloy surfaces in vitro and in vivo. In our previous studies, we demonstrated the chemical presence of doxycycline layer in vitro. In this study, we examined its physical presence using field emission scanning electron microscope and confocal microscope. We also analyzed its controlled released manner using Nano-Drop UV Vis spectrometer. After in vitro characterization of the coating layer, we evaluated its effects on the implant osseointegration in dogs and rabbits. The histological and histomorphometrical results exhibited no significant difference between doxycycline coated and uncoated groups regarding the implants osseointegration and biocompatibility for dental applications. Therefore, coating a doxycycline layer on TiZr implants could be favorable for reducing or removing the antibiotics oral administration after the implantation surgery.

• Pham, Thi Ngoc Maria Huong; Haugen, Håvard Jostein; Rinna, Alessandra; Ellingsen, Jan Eirik & Reseland, Janne Elin (2019). Hydrofluoric acid treatment of titanium surfaces enhance the proliferation of human gingival fibroblasts. Journal of Tissue Engineering. 10. doi: 10.1177/2041731419828950. Full text in Research Archive Show summary

  The attachment of implants rely on bone and soft tissue biocompatibility. The aim was to investigate the effect of fluoride modified metallic titanium (Ti) surfaces (Ti-F) on proliferation and differentiation of human gingival fibroblasts (HGF). HGF cells were exposed to hydrofluoric acid (HF) modified Ti coins (Ti-F) for 1, 3, 7, 14 and 21d, and untreated coins were used as controls. A 5-6 fold increase in the proliferation of HGF on Ti-F compared to Ti surfaces was observed. Enhanced gene expression of IL-6 and OPG was found at 7 d. Increased levels of sclerostin, IL- 6 and OPG in the media from HGF cultured on Ti-F coins were found compared to controls. Our results confirm that HF modified surface may indirectly enhance the firm attachment of implant surface to junction epithelium, soft tissue epithelium, which would give protection for underlying osseous structures making osseointegration of the dental implant possible.

• Brunetti, Giacomina; Belisario, DC; Bortolotti, Sara; Storlino, Giuseppina; Colaianni, Graziana & Faienza, Maria F [Show all 22 contributors for this article] (2019). LIGHT/TNFSF14 Promotes Osteolytic Bone Metastases in Non-small Cell Lung Cancer Patients. Journal of Bone and Mineral Research. ISSN 0884-0431. 35(4), p. 671–680. doi: 10.1002/jbmr.3942. Full text in Research Archive
• Pullisaar, Helen; Colaianni, Graziana; Lian, Aina-Mari; Vandevska-Radunovic, Vaska; Grano, Maria & Reseland, Janne Elin (2019). Irisin promotes growth, migration and matrix formation in human periodontal ligament cells. Archives of Oral Biology. ISSN 0003-9969. doi: 10.1016/j.archoralbio.2019.104635. Full text in Research Archive Show summary

  Objective The objective of the study was to examine the effect of irisin on human periodontal ligament cells (hPDLCs) growth, migration and osteogenic behaviour in vitro. Materials and methods Primary hPDLCs and human osteoblasts (hOBs), used as positive controls, were cultured with irisin (10 and 100 ng/ml), and effect on cell proliferation was evaluated with 5-bromo-2`-deoxyuridine incorporation at 1, 2, and 3 days, and on migration capacity was investigated by scratch assay at 2, 6, and 24 h. Osteogenic behaviour was assessed with alkaline phosphatase activity, immunoassay at 3, 7, 14, and 21 days, and confocal laser scanning microscopy at 21 days. Mineralization was examined by Alizarin red staining at 21 days. Data were compared group wise using ANOVA tests. Results Irisin induced increased proliferation of primary hPDLCs and hOBs at all time points compared to untreated controls. This was confirmed by scratch assay where irisin enhanced migration of both hPDLCs and hOBs after 6 and 24 h compared to controls. Irisin treatment promoted osteogenic behaviour of both cell types by enhancement of extracellular matrix formation. In hPDLCs irisin increased expression of type I collagen, secretion of osteoblastogenesis related proteins osteocalcin and leptin, and calcium deposition/mineralization compared to controls at 21 days. In addition, to enhance calcium deposition/mineralization in hOBs, irisin increased expression of periostin, and secretion of osteoblastogenesis related proteins osteopontin, alkaline phosphatase and osteocalcin, as compared to controls at 21 days. Conclusions Primary hPDLCs responded to irisin treatment with enhanced cell growth, migration, and matrix formation in vitro.

• Gamage, Thilini Hansamali Gamage Yaddehi; Lengle, Emma; Gunnes, Gjermund; Pullisaar, Helen; Holmgren, Asbjørn & Reseland, Janne Elin [Show all 16 contributors for this article] (2019). STIM1 R304W in mice causes subgingival hair growth and an increased fraction of trabecular bone. Cell Calcium. ISSN 0143-4160. 85. doi: 10.1016/j.ceca.2019.102110. Full text in Research Archive
• Zhu, Hao; Xiongfa, Ji; Hanfeng, Guan; Liming, Zhao; Libo, Zhao & Changyu, Liu [Show all 12 contributors for this article] (2019). Tantalum Nanoparticles Reinforced Polyetheretherketone Shows Enhanced Bone Formation. Materials Science and Engineering C: Materials for Biological Applications. ISSN 0928-4931. 101, p. 232–242. doi: 10.1016/j.msec.2019.03.091. Full text in Research Archive Show summary

  Polyetheretherketone (PEEK) has been used in orthopedic surgery for several decades. Numerous methods were invented to alter the property of PEEK. By adding nanoparticles, fibers, elastic modulus and strength of PEEK can be changed to meet certain demand. In this study, tantalum (Ta), a promising metal, was introduced to modify the properties of PEEK, in which PEEK was reinforced with different contents of tantalum nanoparticles (from 1%wt to 9%wt). Mechanical properties and biological functions (both in vitro and in vivo) were then investigated. The highest elastic modulus and compressive strength were observed in 3%Ta-PEEK. Cell experiments as cell adhesion, collagen secretion, biomineralization and osteogenesis related gene expression showed preferable results in 3%Ta-PEEK and 5%Ta-PEEK. Improved bone integration was shown in 3%Ta-PEEK and 5%Ta-PEEK in vivo. Above all, enhanced mechanical properties and promoted bone formation were proved for 3%Ta-PEEK and 5%Ta-PEEK compared to others groups both in vivo and in vitro, suggesting that the addition of tantalum nanoparticles modified the osseointegration ability of PEEK. This composite of tantalum and PEEK could have a clinical potential for orthopedic implants.

• Giannobile, William V; Berglundh, Tord; Al-Nawas, Bilal; Araujo, Mauricio; Bartold, P Mark & Bouchard, Philippe [Show all 18 contributors for this article] (2019). Biological factors involved in alveolar bone regeneration: Consensus report of Working Group 1 of the 15th European Workshop on Periodontology on Bone Regeneration. Journal of Clinical Periodontology. ISSN 0303-6979. 46(S21), p. 6–11. doi: 10.1111/jcpe.13130. Full text in Research Archive
• Mann, Vivek; Grimm, Daniela; Corydon, Thomas J.; Krüger, Marcus; Wehland, Markus & Riwaldt, Stefan [Show all 14 contributors for this article] (2019). Changes in human foetal osteoblasts exposed to the random positioning machine and bone construct tissue engineering. International Journal of Molecular Sciences. ISSN 1661-6596. 30(6). doi: 10.3390/ijms20061357. Full text in Research Archive Show summary

  Human cells, when exposed to both real and simulated microgravity (s-µg), form 3D tissue constructs mirroring in vivo architectures (e.g., cartilage, intima constructs, cancer spheroids and others). In this study, we exposed human foetal osteoblast (hFOB 1.19) cells to a Random Positioning Machine (RPM) for 7 days and 14 days, with the purpose of investigating the effects of s-µg on biological processes and to engineer 3D bone constructs. RPM exposure of the hFOB 1.19 cells induces alterations in the cytoskeleton, cell adhesion, extra cellular matrix (ECM) and the 3D multicellular spheroid (MCS) formation. In addition, after 7 days, it influences the morphological appearance of these cells, as it forces adherent cells to detach from the surface and assemble into 3D structures. The RPM-exposed hFOB 1.19 cells exhibited a differential gene expression of the following genes: transforming growth factor beta 1 (TGFB1, bone morphogenic protein 2 (BMP2), SRY-Box 9 (SOX9), actin beta (ACTB), beta tubulin (TUBB), vimentin (VIM), laminin subunit alpha 1 (LAMA1), collagen type 1 alpha 1 (COL1A1), phosphoprotein 1 (SPP1) and fibronectin 1 (FN1). RPM exposure also induced a significantly altered release of the cytokines and bone biomarkers sclerostin (SOST), osteocalcin (OC), osteoprotegerin (OPG), osteopontin (OPN), interleukin 1 beta (IL-1β) and tumour necrosis factor 1 alpha (TNF-1α). After the two-week RPM exposure, the spheroids presented a bone-specific morphology. In conclusion, culturing cells in s-µg under gravitational unloading represents a novel technology for tissue-engineering of bone constructs and it can be used for investigating the mechanisms behind spaceflight-related bone loss as well as bone diseases such as osteonecrosis or bone injuries.

• Printzell, Lisa; Reseland, Janne Elin; Edin, Nina Frederike J & Ellingsen, Jan Eirik (2019). Effects of ionizing irradiation and interface backscatter on human mesenchymal stem cells cultured on titanium surfaces. European Journal of Oral Sciences. ISSN 0909-8836. 127(6), p. 500–507. doi: 10.1111/eos.12654. Full text in Research Archive Show summary

  Radiotherapy to the head and neck region negatively influences the osseointegration and survival of dental implants. The effects of cobalt 60 (60Co) ionizing radiation and the impact of backscatter rays were investigated on human mesenchymal stem cells cultured on titanium surfaces. Bone marrow‐derived human mesenchymal stem cells were seeded on titanium (Ti), fluoride‐modified titanium (TiF), and tissue culture plastic. Cells were exposed to ionizing γ ‐radiation in single doses of 2, 6, or 10 Gy using a 60Co source. Density and distribution of cells were evaluated using confocal laser‐scanning microscopy, 21 d post‐irradiation. Lactate dehydrogenase concentration and the levels of total protein and cytokines/chemokines were measured in the cell‐culture medium on days 1, 3, 7, 14, and 21 post‐irradiation. Unirradiated cells were used as the control. Irradiation had no effect on cell viability, collagen and actin expression, or cell distribution, but induced an initial increase in the secretion of interleukin (IL )‐6, IL ‐8, monocyte chemotactic protein 1 (MCP ‐1), and vascular endothelial growth factor (VEGF ), followed by a decrease in secretion after 3 or 7 d. Irradiation resulted in secretion of a lower amount of all analytes examined compared with controls on day 21, irrespective of radiation dose and growth surface. Backscattering from titanium did not influence the cell response significantly, suggesting a clinical potential for achieving successful osseointegration of dental implants placed before radiotherapy.

• Colaianni, Graziana; Lippo, Luciana; Sanesi, Lorenzo; Brunetti, Giacomina; Celi, Monica & Cirulli, Nunzio [Show all 13 contributors for this article] (2018). Deletion of the Transcription Factor PGC-1? in Mice Negatively Regulates Bone Mass. Calcified Tissue International. ISSN 0171-967X. doi: 10.1007/s00223-018-0459-4. Full text in Research Archive Show summary

  Peroxisome proliferator-activated receptor-gamma coactivator (PGC1α) is a transcription coactivator that interacts with a broad range of transcription factors involved in several biological responses. Here, we show that PGC1α plays a role in skeletal homeostasis since aged PGC1α-deficient mice (PGC1α−/−) display impaired bone structure. Micro-CT of the tibial mid-shaft showed a marked decrease of cortical thickness in PGC1α−/− (− 11.9%, p < 0.05) mice compared to wild-type littermate. Trabecular bone was also impaired in knock out mice which displayed lower trabecular thickness (Tb.Th) (− 5.9% vs PGC1α+/+, p < 0.05), whereas trabecular number (Tb.N) was higher than wild-type mice (+ 72% vs PGC1α+/+, p < 0.05), thus resulting in increased (+ 31.7% vs PGC1α+/+, p < 0.05) degree of anisotropy (DA), despite unchanged bone volume fraction (BV/TV). Notably, these impairments of cortical and trabecular bone led to a dramatic ~ 48.4% decrease in bending strength (p < 0.01). These changes in PGC1α−/− mice were paralleled by a significant increase in osteoclast number at the cortical bone surface and in serum level of the bone resorption marker, namely, C-terminal cross-linked telopeptides of type I collagen (CTX-I). We also found that in cortical bone, there was lower expression of mRNA codifying for the key bone-building protein Osteocalcin (Ocn). Interestingly, Collagen I mRNA expression was reduced in mesenchymal stem cells from bone marrow of PGC1α−/−, thus indicating that differentiation of osteoblast lineage is downregulated. Overall, results presented herein suggest that PGC1α may play a key role in bone metabolism.

• Haugen, Sigrid; He, Jianying; Sundaresan, Alamelu; Stunes, Astrid Kamilla; Aasarød, Kristin Matre & Tiainen, Hanna [Show all 9 contributors for this article] (2018). Adiponectin reduces bone stiffness; verified in a 3D artificial human bone model in vitro. Frontiers in Endocrinology. 9:236, p. 1–12. doi: 10.3389/fendo.2018.00236. Full text in Research Archive Show summary

  Primary human osteoblasts and osteoclasts incubated in a rotating coculture system without any scaffolding material, form bone-like tissue that may be used to evaluate effects of various compounds on mechanical strength. Circulating adiponectin has been found to be negatively associated with BMD and strength and was therefore assessed in this system. Osteospheres of human osteoblasts and osteoclasts were generated with and without adiponectin. The osteospheres were scanned using micro-computed tomography, the mechanical properties were tested by flat punch compression using nanoindentation equipment, and the cellular morphology characterized by microscopy. The association between autologously produced adiponectin and biomechanical properties was further evaluated by quantitation of adiponectin levels using quantitative polymerase chain reaction (qPCR) and immunoassays, and identification of stiffness by bending test of rat femurs. The molecular mechanisms were examined in vitro using human bone cells. Mechanical testing revealed that adiponectin induced a more compliant osteosphere compared with control. The osteospheres had a round, lobulated appearance with morphologically different areas; inner regions containing few cells embedded in a bone-like material surrounded by an external area with a higher cell quantity. The expression of adiponectin was found to correlate positively to ultimate bending moment and ultimate energy absorption and deflection, on the other hand, it correlated negatively to bending stiffness, indicating autocrine and/or paracrine effects of adiponectin in bone. Adiponectin enhanced proliferation and expression of collagen, leptin, and tumor necrosis factor-alpha in osteoblasts and stimulated proliferation, but not the functional activity of osteoclasts. Our results indicate that both administration of adiponectin during osteosphere production and in situ elevated levels of adiponectin in rat femurs, reduced stiffness of the bone tissues. An increase in undifferentiated cells and extracellular matrix proteins, such as collagen, may explain the reduced bone stiffness seen in the osteospheres treated with adiponectin.

• Stakkestad, Øystein; Heyward, Catherine Anne; Lyngstadaas, Ståle Petter; Medin, Tirill; Vondrasek, Jiri & Lian, Aina-Mari [Show all 8 contributors for this article] (2018). An ameloblastin C-terminus variant is present in human adipose tissue. Heliyon. 4(12). doi: 10.1016/j.heliyon.2018.e01075. Full text in Research Archive Show summary

  Objective: Transcriptional regulatory elements in the ameloblastin (AMBN) promoter indicate that adipogenesis may influence its expression. The objective here was to investigate if AMBN is expressed in adipose tissue, and have a role during differentiation of adipocytes. Design: AMBN expression was examined in adipose tissue and adipocytes by real-time PCR and ELISA. Distribution of ameloblastin was investigated by immunofluorescence in sections of human subcutaneous adipose tissue. The effect of recombinant proteins resembling AMBN and its processed products on proliferation of primary human pre-adipocytes and murine 3T3-L1 cell lines was measured by [3H]-thymidine incorporation. The effect on adipocyte differentiation was evaluated by the expression profile of the adipogenic markers PPARγ and leptin, and the content of lipids droplets (Oil-Red-O staining). Results: AMBN was found to be expressed in human adipose tissue, human primary adipocytes, and in 3T3-L1 cells. The C-terminus of the AMBN protein and a 45 bp shorter splice variant was identified in human subcutaneous adipose tissue. The expression of AMBN was found to increase four-fold during differentiation of 3T3-L1 cells. Administration of recombinant AMBN reduced the proliferation, and enhanced the expression of PPARγ and leptin in 3T3-L1 and human pre-adipocytes, respectively. Conclusions: The AMBN C-terminus variant was identified in adipocytes. This variant may be encoded from a short splice variant. Increased expression of AMBN during adipogenesis and its effect on adipogenic factors suggests that AMBN also has a role in adipocyte development.

• Shabestari, Maziar; Kise, Nina Jullum; Landin, Maria Augusta Dos S Silva; Sessing, Sølve; Hellund, Johan Castberg & Reseland, Janne Elin [Show all 8 contributors for this article] (2018). Enhanced angiogenesis and increased bone turnover characterize bone marrow lesions in osteoarthritis at the base of the thumb. Bone and Joint Research. ISSN 2046-3758. 7(6), p. 406–413. doi: 10.1302/2046-3758.76.BJR-2017-0083.R3. Full text in Research Archive Show summary

  Objectives Little is known about tissue changes underlying bone marrow lesions (BMLs) in non-weight-bearing joints with osteoarthritis (OA). Our aim was to characterize BMLs in OA of the hand using dynamic histomorphometry. We therefore quantified bone turnover and angiogenesis in subchondral bone at the base of the thumb, and compared the findings with control bone from hip OA. Methods Patients with OA at the base of the thumb, or the hip, underwent preoperative MRI to assess BMLs, and tetracycline labelling to determine bone turnover. Three groups were compared: trapezium bones removed by trapeziectomy from patients with thumb base OA (n = 20); femoral heads with (n = 24); and those without (n = 9) BMLs obtained from patients with hip OA who underwent total hip arthroplasty. Results All trapezium bones demonstrated MRI-defined BMLs. Compared with femoral heads without BMLs, the trapezia demonstrated significantly higher bone turnover (mean sd 0.2 (0.1) versus 0.01 (0.01) µm3/µm2/day), mineralizing surface (18.5% (13.1) versus 1.4% (1.3)) and vascularity (5.2% (1.1) versus 1.2% (0.6)). Femoral heads with BMLs exhibited higher bone turnover (0.3 (0.2) versus 0.2 (0.1) µm3/µm2/day), a higher mineralization rate (26.6% (10.6) versus 18.6% (11.9)) and greater trabecular thickness (301.3 µm (108) versus 163.6 µm (24.8)) than the trapezia. Conclusion Bone turnover and angiogenesis were enhanced in BMLs of both the thumb base and hip OA, of which the latter exhibited the highest bone turnover. Thus, the increase in bone turnover in weight-bearing joints like the hip may be more pronounced than less mechanically loaded osteoarthritic joints demonstrating BMLs. The histological changes observed may explain the water signal from BMLs on MRI.

• Hussain, Badra; Thieu, Minh Khai Le; Johnsen, Gaute Floer; Reseland, Janne Elin & Haugen, Håvard Jostein (2017). Can CAD/CAM resin blocks be considered as substitute for conventional resins? Dental Materials. ISSN 0109-5641. 33(12), p. 1362–1370. doi: 10.1016/j.dental.2017.09.003. Full text in Research Archive Show summary

  Objective Dentists are facing a myriad of new CAD/CAM product for dental filling therapies. Are the new materials any worthwhile using? Are they succeeding the standard filling materials? Here we compare for the first time the new resin-composite blocks (RCBs) with conventional materials (Filtek Z250 and Tetric EvoCeram). Methods The material were tested for residual monomer elution by HPLC, thermogravimetric analysis (TG) was used to determine the percentage of fillers by weight, hardness was evaluated by Vickers method, morphology of fillers and distribution in the matrix were examined by scanning electron microscopy (SEM), elemental analysis for elemental determination of the filler particles was performed by energy-dispersive X-ray spectroscopy (EDX) cytotoxicity using human gingival fibroblasts and an epithelial cell line. Results The RBC outperformed conventional composite regarding mechanical characteristics (hardness) and monomer eluation, but showed some worrisome results regarding cytotoxicity. Significance The cost benefit is not in favour of RBCs in comparison to conventional composites, as the cytotoxicity was found higher for RBCs.

• Johnsen, Gaute Floer; Thieu, Minh Khai Le; Hussain, Badra; Pamula, Elzbieta; Reseland, Janne Elin & Lyngstadaas, Ståle Petter [Show all 7 contributors for this article] (2017). Own brand label restorative materials - A false bargain? Journal of Dentistry. ISSN 0300-5712. 56, p. 84–98. doi: 10.1016/j.jdent.2016.11.004. Full text in Research Archive Show summary

  Objectives This study aims at evaluating and comparing mechanical, chemical, and cytotoxicological parameters of a commercial brand name composite material against two ‘own brand label' (OBL) composites. Methods Parameters included depth of cure, flexural strength, degree of conversion, polymerization shrinkage, filler particle morphology and elemental analyses, Vickers hardness, surface roughness parameters after abrasion, monomer elution, and cytotoxicity. Results The conventional composite outperformed the OBLS in terms of depth of cure (p < 0.001), degree of cure at the first and last time intervals (p < 0.001), hardness (p < 0.001), and post-abrasion roughness (p < 0.05). The polymerization volumetric shrinkage ranged from 2.86% to 4.13%, with the highest shrinkage seen among the OBLs. Both Monomer elution from the OBLs was statistically significantly higher (p<0.001). Statistically significantly higher cytotoxicity combined with altered morphology and loss of confluence was detected in the cells exposed to extracts from the OBLs. Conclusions The OBLs were in general outdone by the conventional composite. Clinical Significance: OBLs restorative materials have become pervasive in the dental market. Manufacturers often promise equal or better characteristics than existing brand-name composites, but at a lower price. Dentists are highly recommended to reconsider utilization of OBLs lacking sound scientific scrutiny, and our findings underscore this recommendation

• Colaianni, Graziana; Lippo, Luciana; Pignataro, Paolo; Sanesi, Lorenzo; Severi, Ilenia & Brunetti, Giacomina [Show all 11 contributors for this article] (2017). Treatment with r-irisin prevents and recovers disuse-induced bone loss and muscle atrophy. Italian Journal of Anatomy and Embryology. ISSN 2038-5129. 122(1), p. 64–64. Full text in Research Archive
• Brunetti, Giacomina; Lippo, Luciana; Storlino, Giuseppina; Gigante, Isabella; Colaianni, Graziana & Benedetto, Adriana Di [Show all 15 contributors for this article] (2017). LIGHT/TNFSF14 deficiency affects basal bone remodeling through the regulation of osteoprotegerin expression. Journal of Bone and Mineral Research. ISSN 0884-0431. 32, p. 273–274. doi: 10.1002/jbmr.3345. Full text in Research Archive
• Colaianni, Graziana; Lippo, Luciana; Pignataro, Paolo; Sanesi, Lorenzo; Spiro, Giovanna & Severi, Ilenia [Show all 14 contributors for this article] (2017). Unloaded Mice Treated with the Myokine Irisin Are Protected from Bone Loss and Muscle Atrophy. Journal of Bone and Mineral Research. ISSN 0884-0431. 32, p. 76–76. Full text in Research Archive
• Stakkestad, Øystein; Lyngstadaas, Ståle Petter; Vondrášek, Jiří; Gordeladze, Jan Oxholm & Reseland, Janne Elin (2017). Ameloblastin peptides modulates the osteogenic capacity of human mesenchymal stem cells. Frontiers in Physiology. 8. doi: 10.3389/fphys.2017.00058. Full text in Research Archive Show summary

  During amelogenesis the extracellular enamel matrix protein AMBN is quickly processed into 17 kDa (N-terminus) and 23 kDa (C-terminus) fragments. In particular, alternatively spliced regions derived by exon 5/6 within the N-terminus region are known to be critical in biomineralization. Human mesenchymal stem cells (hMSC) also express and secrete AMBN, but it is unclear if this expression has effects on the hMSC themselves. If, as suggested from previous findings, AMBN act as a signaling molecule, such effects could influence hMSC growth and differentiation, as well as promoting the secretion of other signaling proteins like cytokines and chemokines. If AMBN is found to modulate stem cell behavior and fate, it will impact our understanding on how extracellular matrix molecules can have multiple roles during development ontogenesis, mineralization and healing of mesenchymal tissues. Here we show that synthetic peptides representing exon 5 promote hMSC proliferation. Interestingly, this effect is inhibited by the application of a 15 aa peptide representing the alternatively spliced start of exon 6. Both peptides also influence gene expression of RUNX2 and osteocalcin, and promote calcium deposition in cultures, indicating a positive influence on the osteogenic capacity of hMSC. We also show that the full-length AMBN-WT and N-terminus region enhance the secretion of RANTES, IP-10, and IL-8. In contrast, the AMBN C-terminus fragment and the exon 5 deleted AMBN (DelEx5) have no detectable effects on any of the parameters investigated. These findings suggest the signaling effect of AMBN is conveyed by processed products, whereas the effect on proliferation is differentially modulated through alternative splicing during gene expression.

• Brunetti, Giacomina; Faienza, MF; Colaianni, Graziana; Gigante, Isabella; Oranger, Angela & Pignataro, Paolo [Show all 21 contributors for this article] (2017). Impairment of bone remodeling in LIGHT/TNFSF14-deficient mice. Journal of Bone and Mineral Research. ISSN 0884-0431. 33(4), p. 704–719. doi: 10.1002/jbmr.3345. Full text in Research Archive
• Stakkestad, Øystein; Lyngstadaas, Ståle Petter; Thiede, Bernd; Vondrasesek, Jiri; Skålhegg, Bjørn Steen & Reseland, Janne Elin (2017). Phosphorylation Modulates Ameloblastin Self-assembly and Ca2+ Binding. Frontiers in Physiology. 8. doi: 10.3389/fphys.2017.00531. Full text in Research Archive Show summary

  Ameloblastin (AMBN), an important component of the self-assembled enamel extra cellular matrix, contains several in silico predicted phosphorylation sites. However, to what extent these sites actually are phosphorylated and the possible effects of such post-translational modifications are still largely unknown. Here we report on in vitro experiments aimed at investigating what sites in AMBN are phosphorylated by casein kinase 2 (CK2) and protein kinase A (PKA) and the impact such phosphorylation has on self-assembly and calcium binding. All predicted sites in AMBN can be phosphorylated by CK2 and/or PKA. The experiments show that phosphorylation, especially in the exon 5 derived part of the molecule, is inversely correlated with AMBN self-assembly. These results support earlier findings suggesting that AMBN self-assembly is mostly dependent on the exon 5 encoded region of the AMBN gene. Phosphorylation was significantly more efficient when the AMBN molecules were in solution and not present as supramolecular assemblies, suggesting that post-translational modification of AMBN must take place before the enamel matrix molecules self-assemble inside the ameloblast cell. Moreover, phosphorylation of exon 5, and the consequent reduction in self-assembly, seem to reduce the calcium binding capacity of AMBN suggesting that post-translational modification of AMBN also can be involved in control of free Ca2+ during enamel extra cellular matrix biomineralization. Finally, it is speculated that phosphorylation can provide a functional crossroad for AMBN either to be phosphorylated and act as monomeric signal molecule during early odontogenesis and bone formation, or escape phosphorylation to be subsequently secreted as supramolecular assemblies that partake in enamel matrix structure and mineralization.

• Haugen, Sigrid; Aasarød, Kristin Matre; Stunes, Astrid Kamilla; Mosti, Mats Peder; Franzen, Tanya Jeanette & Vandevska-Radunovic, Vaska [Show all 8 contributors for this article] (2017). Adiponectin prevents orthodontic tooth movement in rats. Archives of Oral Biology. ISSN 0003-9969. 83, p. 304–311. doi: 10.1016/j.archoralbio.2017.08.009. Full text in Research Archive Show summary

  Objective The objective was to examine the effects of repetitive local administration of adiponectin on experimental tooth movement in rats. Materials and methods The maxillary right first molar of male Wistar rats (n = 24) was moved mesially for 14 days, with local adiponectin injections (0.2 or 2 μg) every third day. Micro-computed tomography was performed at days 0, 6 and 14 and molar movement, bone density and bone volume fraction were calculated from the scans. Changes in extracellular matrix collagen and cell numbers in the periodontal ligament were analyzed histologically, and levels of circulating cytokines were measured by Luminex and ELISA. Results Adiponectin injections induced a reduction in tooth movement after 12 and 14 days compared to controls. No tooth movement was observed between days 3 and 14 in the group receiving the highest dosage (2 μg) of adiponectin. Differences in bone density and bone volume fractions between treatment and control groups were not identified. Relative size and morphology of collagen fibrils, and cell number in the periodontal region after adiponectin injections were unchanged compared to controls. Levels of circulating adiponectin or other selected factors in plasma were not influenced by the adiponectin injections. Conclusions Submucosal injections of adiponectin prevented experimental tooth movement in rats. The effect was dosage-dependent and local. Adiponectin injections caused no detectable changes in bone density, periodontal cell number or collagen content.

• Colaianni, Graziana; Mongelli, Teresa; Cuscito, Concetta; Pignataro, Paolo; Lippo, Luciana & Spiro, Giovanna [Show all 18 contributors for this article] (2017). Irisin prevents and restores bone loss and muscle atrophy in hind-limb suspended mice. Scientific Reports. 7(1). doi: 10.1038/s41598-017-02557-8. Full text in Research Archive Show summary

  We previously showed that Irisin, a myokine released from skeletal muscle after physical exercise, plays a central role in the control of bone mass. Here we report that treatment with recombinant Irisin prevented bone loss in hind-limb suspended mice when administered during suspension (preventive protocol) and induced recovery of bone mass when mice were injected after bone loss due to a suspension period of 4 weeks (curative protocol). MicroCT analysis of femurs showed that r-Irisin preserved both cortical and trabecular bone mineral density, and prevented a dramatic decrease of the trabecular bone volume fraction. Moreover, r-Irisin protected against muscle mass decline in the hind-limb suspended mice, and maintained the fiber cross-sectional area. Notably, the decrease of myosin type II expression in unloaded mice was completely prevented by r-Irisin administration. Our data reveal for the first time that Irisin retrieves disuse‐induced bone loss and muscle atrophy. These findings may lead to development of an Irisin-based therapy for elderly immobile osteoporotic and physically disable patients, and might represent a countermeasure for astronauts subjected to microgravity-induced bone and muscle losses.

• Olsen-Bergem, Heming; Kristoffersen, Anne Karin; Bjørnland, Tore; Reseland, Janne Elin & Aas, Jørn Arne (2016). Juvenile idiopathic arthritis and rheumatoid arthritis: Bacterial diversity in temporomandibular joint synovial fluid in comparison with immunological and clinical findings. International Journal of Oral & Maxillofacial Surgery. ISSN 0901-5027. 45(3), p. 318–322. doi: 10.1016/j.ijom.2015.08.986. Full text in Research Archive
• Wiig, Elisabeth; Reseland, Janne Elin; Østbye, Kjartan; Haugen, Håvard Jostein & Vøllestad, Leif Asbjørn (2016). Variation in Lateral Plate Quality in Threespine Stickleback from Fresh, Brackish and Marine Water: A Micro-Computed Tomography Study. PLOS ONE. 11(10). doi: 10.1371/journal.pone.0164578. Full text in Research Archive Show summary

  Introduction It is important to understand the drivers leading to adaptive phenotypic diversity within and among species. The threespine stickleback (Gasterosteus aculeatus) has become a model system for investigating the genetic and phenotypic responses during repeated colonization of fresh waters from the original marine habitat. During the freshwater colonization process there has been a recurrent and parallel reduction in the number of lateral bone plates, making it a suitable system for studying adaptability and parallel evolution. Objective The aim of this study was to investigate an alternative evolutionary path of lateral plate reduction, where lateral plates are reduced in size rather than number. Materials and Methods A total of 72 threespine stickleback individuals from freshwater (n = 54), brackish water (n = 27) and marine water (n = 9) were analysed using microcomputed tomography (μCT) to determine variation in size, thickness and structure of the lateral plates. Furthermore, whole-body bone volume, and bone volume, bone surface and porosity of lateral plate number 4 were quantified in all specimens from each environment. Results The results showed a significant difference in plate size (area and volume) among populations, where threespine stickleback from polymorphic freshwater and brackish water populations displayed lateral plates reduced in size (area and volume) compared to marine stickleback Conclusions Reduction of lateral plates in threespine stickleback in fresh and brackish water occurs by both plate loss and reduction in plate size (area and volume).

• Grimm, Daniela; Grosse, Jirka; Wehland, Markus; Mann, Vivek; Reseland, Janne Elin & Sundaresan, Alamelu [Show all 7 contributors for this article] (2016). The impact of microgravity on bone in humans. Bone. ISSN 8756-3282. 87, p. 44–56. doi: 10.1016/j.bone.2015.12.057. Full text in Research Archive
• Aasarød, Kristin Matre; Ramezanzadehkoldeh, Masoud; Shabestari, Maziar; Mosti, Mats Peder; Stunes, Astrid Kamilla & Reseland, Janne Elin [Show all 15 contributors for this article] (2016). Skeletal effects of a gastrin receptor antagonist in H+/K+ATPase beta subunit KO mice. Journal of Endocrinology. ISSN 0022-0795. 230(2), p. 251–262. doi: 10.1530/JOE-16-0017. Full text in Research Archive
• Villa, Oscar; Wohlfahrt, Johan Caspar; Koldsland, Odd Carsten; Brookes, Steven J; Lyngstadaas, Ståle Petter & Aass, Anne Merete [Show all 7 contributors for this article] (2016). EMD in periodontal regenerative surgery modulates cytokine profiles: A randomised controlled clinical trial. Scientific Reports. 6, p. 1–9. doi: 10.1038/srep23060. Full text in Research Archive Show summary

  The enamel matrix derivative (EMD) contains hundreds of peptides in different levels of proteolytic processing that may provide a range of biological effects of importance in wound healing. The aim of the present study was to compare the effect of EMD and its fractions on the cytokine profiles from human gingival fibroblasts in vitro and in gingival crevicular fluid (GCF) in a randomized controlled split-mouth clinical study (n = 12). Levels of cytokines in cell culture medium and in GCF were measured by Luminex over a 2-week period. In the clinical study, levels of pro-inflammatory cytokines and chemokines were increased, whereas the levels of transforming growth factor-α (TGF-α) and platelet-derived growth factor-BB (PDGF-BB) were reduced. The in vitro study showed that EMD and its high and low molecular weight fractions reduced the secretion of pro-inflammatory cytokines and chemokines compared to untreated cells. EMD had an effect on levels of cytokines related to fibroplasia, angiogenesis, inflammation and chemotaxis both in vitro and in vivo, however, the anti-inflammatory effect induced by EMD observed in the in vitro study could not be confirmed clinically.

• Kruger, Tormod Bjartveit; Herlofson, Bente Brokstad; Landin, Maria Augusta Dos S Silva & Reseland, Janne Elin (2016). Alendronate alters osteoblast activities. Acta Odontologica Scandinavica. ISSN 0001-6357. 74(7), p. 550–557. doi: 10.1080/00016357.2016.1217041. Full text in Research Archive
• Shabestari, Maziar; Vik, Jarle; Reseland, Janne Elin & Eriksen, Erik Fink (2016). Bone marrow lesions in hip osteoarthritis are characterized by increased bone turnover and enhanced angiogenesis. Osteoarthritis and Cartilage. ISSN 1063-4584. 24(10), p. 1745–1752. doi: 10.1016/j.joca.2016.05.009. Full text in Research Archive
• Aasarød, Kristin Matre; Mosti, Mats Peder; Stunes, Astrid Kamilla; Reseland, Janne Elin; Basso, Trude & Syversen, Unni [Show all 7 contributors for this article] (2016). Impaired skeletal health in patients with chronic atrophic gastritis. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 51(7), p. 774–781. doi: 10.3109/00365521.2016.1141317. Full text in Research Archive
• Aasarød, Kristin Matre; Stunes, Astrid Kamilla; Mosti, Mats Peder; Ramezanzadehkoldeh, Masoud; Viggaklev, Bjørn Ivar & Reseland, Janne Elin [Show all 9 contributors for this article] (2016). Effects of the histamine 1 receptor antagonist cetirizine on the osteoporotic phenotype in H+ /K+ ATPase beta subunit KO mice. Journal of Cellular Biochemistry. ISSN 0730-2312. 117(9), p. 2089–2096. doi: 10.1002/jcb.25514. Full text in Research Archive
• Müller, Benjamin; Reseland, Janne Elin; Haugen, Håvard Jostein & Tiainen, Hanna (2015). Cell growth on pore-graded biomimetic TiO2 bone scaffolds. Journal of Biomaterials Applications. ISSN 0885-3282. 29(9), p. 1284–1295. doi: 10.1177/0885328214559859. Full text in Research Archive

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• Mascherin, Elisa; Karlsen, Markus; Wohlmann, Jens; Reseland, Janne Elin & Linke, Dirk (2025). In vitro toxicology and antimicrobial efficacy of Q-FIELD™, an innovative photocatalytic additive for paints. Full text in Research Archive
• Wang, Qidi; Akdeniz, Cennet; Heck, Ansgar; Bjørk, Mai Britt; Theisen, Ole Rasmus & Eggesbø, Heidi Beate [Show all 16 contributors for this article] (2025). X-bundet hypofosfatemi. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 145(3). doi: 10.4045/tidsskr.24.0476. Full text in Research Archive Show summary

  X-bundet hypofosfatemi er en sjelden genetisk sykdom som medfører fosfattap i nyrene, redusert mineralisering av tenner og skjelett, deformerte knokler og begrenset mobilitet. Dette har betydelige konsekvenser for helse og livskvalitet. Denne kliniske oversikten gjennomgår anbefalinger for diagnostisering, behandling og oppfølging av voksne med tilstanden.

• Sikorski, Pawel; Helvoort, Antonius Van; Christiansen, Emil; Vorwald, Charlotte E; Gonzalez-Fernandez, Tomas & Reseland, Janne Elin [Show all 8 contributors for this article] (2022). Spheroid-based model system to study bone mineralization in 3D. Full text in Research Archive
• Rahmati, Maryam; Frank, Matthias Johannes; Walter, Sebastian Martin; Monjo, Marta Cabrer; Satué, Maria & Reseland, Janne Elin [Show all 8 contributors for this article] (2021). Osteo-immune responses to the enamel matrix derivative coating layer on titanium-based implants. Full text in Research Archive
• Zhu, Hao; Ji, Xiongfa; Guan, Hanfeng; Zhao, Liming; Zhao, Libo & Liu, Changyu [Show all 12 contributors for this article] (2021). Corrigendum to “Tantalum nanoparticles reinforced polyetheretherketone shows enhanced bone formation” [Mater. Sci. Eng. C 101 (2019) 232–242] (Materials Science & Engineering C (2019) 101 (232–242), (S0928493118321453), (10.1016/j.msec.2019.03.091)). Materials Science and Engineering C: Materials for Biological Applications. ISSN 0928-4931. 128. doi: 10.1016/j.msec.2021.112332. Full text in Research Archive
• Suslu, Safiyye; Høgestøl, Ingvild Kristine; Eriksen, Erik Fink & Reseland, Janne Elin (2020). Changes in protein profile in bone marrow extracts before and one year after gastric bypass surgery. Bone Reports. 13. doi: 10.1016/j.bonr.2020.100368. Full text in Research Archive
• Haugen, Håvard Jostein; Reseland, Janne Elin & Gomez-Florit, Manuel (2018). The effect of IDP coated biomaterial. Full text in Research Archive
• Haugen, Håvard Jostein & Reseland, Janne Elin (2018). In vivo performance of a highly porous titanium dioxide bone scaffold and its way to the medical device market. Full text in Research Archive
• Syversen, Unni; Mynarek, Ida Maria; Iversen, Trude Seselie Jahr; Eriksen, Erik Fink; Reseland, Janne Elin & Basso, Trude [Show all 10 contributors for this article] (2017). Impaired bone quality, assessed by trabecular bone score and in vivo micro indentation, in men with type 1 diabetes mellitus. Full text in Research Archive
• Sundaresan, Alamelu; Olamigoke, Loretta; Mansoor, Elvedina; Devakottai, Ria; Reseland, Janne Elin & Brungs, Sonja [Show all 12 contributors for this article] (2017). Alleviation of inflammation and stimulation of the immune response by Active Hexose Correlated Compound (AHCC) in stressful physiological environments. Full text in Research Archive
• Gomez-Florit, Manuel; Reseland, Janne Elin & Haugen, Håvard Jostein (2017). Synthetic intrinsically-disordered-peptides for bone tissue engineering. Full text in Research Archive Show summary

  DISCUSSION & CONCLUSIONS: Results show that synthetic IDPs are able to influence hOBs biomineralization. The earlier upregulation of osteogenic markers together with the decreased wound area induced by P2 indicate that it has potential to induce bone regeneration. Bone related proteins, cytokines and chemokines released to culture media are already being analysed to confirm these results. IDPs might be a reliable option to develop new biomaterials and tissue engineering strategies

• Haugen, Håvard Jostein; Johnsen, Gaute Floer; Reseland, Janne Elin; Hussain, Badra & Thieu, Minh Khai Le (2017). Can CAD/CAM Resin Blocks be Considered as a Substitute to Conventional Resins? Full text in Research Archive
• Shabestari, Maziar; Vik, Jarle; Reseland, Janne Elin & Eriksen, Erik Fink (2017). Erratum to "Bone marrow lesions in hip osteoarthritis are characterized by increased bone turnover and enhanced angiogenesis" [Osteoarthritis Cartilage 24 (2016) 1745-1752]. Osteoarthritis and Cartilage. ISSN 1063-4584. 25(4), p. 611–611. doi: 10.1016/j.joca.2016.12.004. Full text in Research Archive

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