This continuation application is directed towards an understanding of how extracellular matrix of bone influences bone formation and resorption. The applicant proposes that osteopontin and proteoglycans control bone formation and resorption. Alterations in phosphorylation, sulfation and covalent crosslinking of these bone matrix proteins may modify the function of these proteins within the bone matrix. Recent published evidence indicates that the bone matrix proteins may have substantial roles in osteoclast and osteoblast function, including the cell adhesion properties of bone cells to hydroxyapatite.
Four specific aims are proposed; first, to assay osteopontin of differing degrees of phosphorylation for effects on in vitro hydroxyapatite formation and growth; second, to evaluate the ability of calcitriol to alter osteopontin expression and phosphorylation. This includes exploring the genomic and nongenomic actions of two calcitriol derivatives on osteopontin expression and post- translation modifications; third, to identify glutamine residues in osteopontin that are substrates for transglutaminase activity and determine if bone cells contain transglutaminase activity; and fourth, to evaluate the role of phosphorylated and nonphosphorlyated forms of osteopontin to mediate bone cell adhesion and function.
| Chang, P L; Lee, T F; Garretson, K et al. (1997) Calcitriol enhancement of TPA-induced tumorigenic transformation is mediated through vitamin D receptor-dependent and -independent pathways. Clin Exp Metastasis 15:580-92 |
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| Chambers, A F; Hota, C; Prince, C W (1993) Adhesion of metastatic, ras-transformed NIH 3T3 cells to osteopontin, fibronectin, and laminin. Cancer Res 53:701-6 |
| Prince, C W (1989) Secondary structure predictions for rat osteopontin. Connect Tissue Res 21:15-20 |
