Biomineralization is a complex process orchestrated by cells, growth factors and a number of key extracellular matrix molecules, and the elucidation of factors that control the formation and maintenance of the functional mineralized matrix is critical in understanding the cause of mineralized tissue disorders. Recent studies have indicated that biglycan (BGN), a member of small leucine rich matrix proteoglycans, plays a role in bone formation/matrix mineralization by modulating osteoblast differentiation. However, the mechanisms are not well understood. This exploratory research is intended to seek a novel modulatory role of BGN in osteoblast differentiation and subsequent matrix mineralization. The hypothesis to be tested is that BGN promotes osteoblast differentiation/matrix mineralization by through its specific interaction with bone morphogenetic protein (BMP)-2. To test this hypothesis the following specific aims will be pursued: (1) to determine the binding specificity of BGN to BMP-2; (2) to investigate the effects of BGN on BMP-2-mediated osteoblastic cell differentiation; and (3) to determine the effects of BGN and BMP-2 on osteoblastic cell differentiation and matrix mineralization using osteoblastic MC3T3-E1 cell-derived clones expressing lower levels of BGN. The data obtained from this study may provide insights into a novel pathway of matrix-modulated osteoblast differentiation and mineralized tissue formation.
| Mochida, Yoshiyuki; Parisuthiman, Duenpim; Pornprasertsuk-Damrongsri, Suchaya et al. (2009) Decorin modulates collagen matrix assembly and mineralization. Matrix Biol 28:44-52 |
| Kamiya, Nobuhiro; Ye, Ling; Kobayashi, Tatsuya et al. (2008) BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway. Development 135:3801-11 |
| Atsawasuwan, Phimon; Mochida, Yoshiyuki; Katafuchi, Michitsuna et al. (2008) Lysyl oxidase binds transforming growth factor-beta and regulates its signaling via amine oxidase activity. J Biol Chem 283:34229-40 |
| Yamauchi, Mitsuo; Shiiba, Masashi (2008) Lysine hydroxylation and cross-linking of collagen. Methods Mol Biol 446:95-108 |
| Kamiya, Nobuhiro; Ye, Ling; Kobayashi, Tatsuya et al. (2008) Disruption of BMP signaling in osteoblasts through type IA receptor (BMPRIA) increases bone mass. J Bone Miner Res 23:2007-17 |
| Kaku, Masaru; Mochida, Yoshiyuki; Atsawasuwan, Phimon et al. (2007) Post-translational modifications of collagen upon BMP-induced osteoblast differentiation. Biochem Biophys Res Commun 359:463-8 |
| Mochida, Yoshiyuki; Parisuthiman, Duenpim; Kaku, Masaru et al. (2006) Nephrocan, a novel member of the small leucine-rich repeat protein family, is an inhibitor of transforming growth factor-beta signaling. J Biol Chem 281:36044-51 |
| Mochida, Yoshiyuki; Parisuthiman, Duenpim; Yamauchi, Mitsuo (2006) Biglycan is a positive modulator of BMP-2 induced osteoblast differentiation. Adv Exp Med Biol 585:101-13 |
