The long-term goal of this study is to understand the regulatory mechanisms of collagen matrix mineralization in bones and teeth. During the last grant period, we have partially characterized the unique aspects of collagen cross-linking, and specific tissue distribution as well as mRNA expression pattern of collagen-binding small leucine-rich proteoglycans (CB-SLRPs) in mineralized tissues. These and other findings have led us to hypothesize: 1. the covalent intermolecular cross-linking of type I collagen is involved in regulating the spatial aspect of mineralization, and 2. a collagen-binding proteoglycan, decorin (DCN), partially regulates the timing and quality of collagen mineralization. To test these hypotheses, we would like: 1a. To establish osteoblastic cell clones that synthesize low levels of lysyl hydroxylase-2 to switch the cross-linking pathway from mineralized to non-mineralized tissue phenotype, 1b. To characterize the lysine hydroxylation and cross-linking chemistries (type, quantity and molecular distribution) of collagen matrix, and the mineralization pattern produced by the clones in vitro and in vivo. 2a. To investigate the roles of DCN in collagen maturation and mineralization in vitro and in vivo by employing overexpression and antisense approaches in osteoblastic cell line. 2b. To characterize the matrix mineralization (collagen and mineral) in bones/dentin in DCN-deficient and DCN/biglycan-double deficient mice. 2c. To evaluate the effects of DCN-collagen interaction on collagen maturation in vitro. The data obtained from this study may provide insights into the regulatory mechanisms of collagen mineralization in bones and teeth. ? ?
| Mochida, Yoshiyuki; Kaku, Masaru; Yoshida, Keiko et al. (2011) Podocan-like protein: a novel small leucine-rich repeat matrix protein in bone. Biochem Biophys Res Commun 410:333-8 |
| Mochida, Yoshiyuki; Parisuthiman, Duenpim; Pornprasertsuk-Damrongsri, Suchaya et al. (2009) Decorin modulates collagen matrix assembly and mineralization. Matrix Biol 28:44-52 |
| Tokutomi, Kentaro; Matsuura, Takashi; Atsawasuwan, Phimon et al. (2008) Characterization of mandibular bones in senile osteoporotic mice. Connect Tissue Res 49:361-6 |
| Nagaoka, Hideaki; Mochida, Yoshiyuki; Atsawasuwan, Phimon et al. (2008) 1,25(OH)2D3 regulates collagen quality in an osteoblastic cell culture system. Biochem Biophys Res Commun 377:674-8 |
| Boushell, Lee W; Kaku, Masaru; Mochida, Yoshiyuki et al. (2008) Immunohistochemical localization of matrixmetalloproteinase-2 in human coronal dentin. Arch Oral Biol 53:109-16 |
| 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 |
| Bedran-Russo, Ana Karina B; Pereira, Patricia N R; Duarte, Wagner R et al. (2008) Removal of dentin matrix proteoglycans by trypsin digestion and its effect on dentin bonding. J Biomed Mater Res B Appl Biomater 85:261-6 |
| Yamauchi, Mitsuo; Shiiba, Masashi (2008) Lysine hydroxylation and cross-linking of collagen. Methods Mol Biol 446:95-108 |
| Verdelis, Kostas; Lukashova, Lyudmilla; Yamauchi, Mitsuo et al. (2007) Changes in matrix phosphorylation during bovine dentin development. Eur J Oral Sci 115:296-302 |
| 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 |
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