Another PhD from the department!
Øystein Stakkestad has publicly defended his doctoral dissertation The role of ameloblastin in mesenchymal tissues. Department of Biomaterials congratulates Øystein on his great achievement!
Ameloblastin, a protein important for dental enamel biomineralisation is expressed in mesenchymal stem cells and has previously been shown to influence the regeneration of mineralised tissues. Ameloblastin self-assembly into fibrillary structures in the enamel matrix, phosphorylation, and interaction with calcium are believed to be important for the function of ameloblastin in mineralising tissues. Ameloblastin is also processed into smaller products that are assumed important for the differentiation and proliferation of stem cells. Expression analysis of the ameloblastin gene also indicates that it is expressed during differentiation of stem cells into adipocytes.
This thesis describes the effects of ameloblastin protein and ameloblastin derived peptides on stem cells differentiating into mineralising cells. The full-length
self-assembled ameloblastin protein has an effect on the secretion of signal molecules important for the recruitment and differentiation of cells involved in bone healing and remodelling. Conversely, single molecule ameloblastin proteins positively affected stem cell maturation and differentiation into mineralising cells.
Ameloblastin expression was also found to increase with differentiation of adipocytes and was found in mature adipose tissue. The C-terminus products have been shown to bind calcium, and the discovery of such variants in adipocytes may indicate unknown roles for calcium in this tissue.
Ameloblastin proteins were phosphorylated in vitro and amino acids carrying phosphate were identified with mass spectrometry. The positioning of the phosphorylated residues within the ameloblastin sequence indicates that phosphorylation may be a way for the cells to control the self-assembly of ameloblastin. Small angle x-ray scattering of proteins either incubated with or without calcium, indicated a structural influence of calcium on self-assembly of ameloblastin.
The self-assembly of ameloblastin into fibrillary structures is known to occur spontaneously. Most of the cell types in which ameloblastin has been identified secrete the molecules into the interstitium. In view of the results presented here one may surmise that self-assembled ameloblastin is complexed with calcium during secretion.
With ameloblastin being present in several types of mesenchymal tissues, phosphorylation at specific residues might be a way for tissues to control whether or
not ameloblastin is secreted as a self-assembled protein with effect on cell maturation or as a molecule carrying calcium to supporting a more mature, mineralising cell type.
- Professor Emeritus Colin Robinson, University of Leeds, UK
- Clinical Associate Professor Axel Spahr, University of Sydney, Australia
- Professor Anne Merete Aass, University of Oslo