Modulation of Dentinogenesis by OP-l Ihrough Type I Bone Morphogenetic Protein Receptors In developing tooth models BMP's 2,4 and 7 (OP-l) have been detected in mature odontoblasts, predentin, ameloblasts and enamel matrix. Transcripts of BMP-7 are abundant in the developing tooth bud. Recombinant OP-l has been shown to be a useful pulp-capping agent, capable of inducing dentin formation on amputated pulp stumps. The amount of reparative dentin formed was proportional to the amount of rOP-l applied suggesting that it may have an important role in dentinogenesis. Alkaline phosphatase has been shown to be an important differentiation marker for both osteoblast and odontoblast cells in vivo and in culture. Although ALP has a clear-cut function, hydrolyzing phosphate ions from organic radicals, its role in mineralization is not fully understood. It is known that BMPs mediate their physiological effects through transmembranous serine/threonine kinase receptors Type I and II which act together as a complex for ligand binding and signal transduction. Phosphorylation occurs in t he GS domain which is conserved in all known Type I receptors. Previous studies have described the expression of developmental/dfflerentiation specific markers which have allowed a preliminary assignation of these cell lines to specific differentiation stages between pulp cell and odontoblast suggesting that the expression of BMP receptors follows a temporal pattern with expression of specific receptors being up or down regulated according to the state of differentiation of the cell. Hypotheses: OP-l is responsible for the proliferation of pulp cells and induces their differentiation into odontoblasts during dentinogenesis in the mouse.
Specific Aims : (1) Determine temporal-spatial expression patterns of ALK 2,3 and 6 in the developing murine tooth bud. (2) Describe cell proliferation alkaline phosphatase expression and mineralization of a pulp and an odontoblast cell lines treated with rOP-1. (3) Establish clonal cell lines expressing truncated ALK2 (BMPR I) and ALK 6 (BMPR IB) receptors in a pulp and an odontoblast cell line, and determine the effects of rOP-1 on cell proliferation, ALP expression and mineralization.
Showing the most recent 10 out of 34 publications
