Sigrid Haugen

• 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.

• 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.

• Gordeladze, Jan Oxholm; Stakkestad, Øystein; Haugen, Sigrid; Reseland, Janne Elin; Syversen, Unni & Johnsen, Gaute Floer [Show all 10 contributors for this article] (2014). Regulatory Loops Consisting of Transcription Factors and MicroRNA Species Determining the Mineralizing Characteristics of Cell Phenotypes - Implications for Bone Engineering and Prevention of Soft Tissue Mineralization. In Eberli, Daniel (Eds.), Cells and Biomaterials in Regenerative Medicine. IntechOpen. ISSN 9789535117315. doi: 10.5772/59149. Full text in Research Archive

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• Gordeladze, Jan Oxholm; Reseland, Janne Elin; Haugen, Håvard Jostein; Haugen, Sigrid; Stakkestad, Øystein & Johnsen, Gaute Floer [Show all 9 contributors for this article] (2014). Epigenetic factors involved in the "mineralizing/demineralizing" capability of cell phenotypes: Histone deacetylaces (HDACs/Sirts), transcription factors (TFs), microRNAs, and vitamin K2 (MK-7). Full text in Research Archive

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