The long term goal of this investigation is to understand the mechanisms regulating the spatial and temporal aspects of collagen mineralization. During the last grant period, partial characterization of the chemical states of collagen cross-linking and the three dimensional structure of the collagen fibrils in relation to mineralization were accomplished. These findings have led to the hypothesis that, in collagen-based mineralized tissues, the orientation and stacking of mineral platelets are spatially regulated by the configuration of the nontriple helical domains (telopeptides) of the type I collagen molecules. In addition, a group of proteoglycans (many of them are collagen-associated proteoglycans) in the tooth have been identified and were found to be immunolocalized almost exclusively in the premineralizing matrices such as near pericementocytes, precementum and predentin. These proteoglycans may be inhibiting premature mineralization through their association with collagen fibrils. By using the tooth (which does not remodel) as the major model, the specific questions asked in this application are: What are the chemical states of the amino- and carboxyl-terminal nontriple helical domains in premineralizing, mineralizing and non (never)-mineralizing collagens? How do these chemical states change with mineralization? What are the structural characteristics of the proteoglycans and their spatial relationship to collagen fibrils in predentin and precementum? and how do they change in mineralizing matrix (dentin and cementum)? In order to address these questions, biochemical, physical, immunochemical and immunohistochemical techniques will be employed. The information obtained from these studies will provide insight into the regulatory mechanisms of collagen mineralization.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE010489-05A1
Application #
2620158
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1993-07-01
Project End
2002-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Dentistry
Type
Schools of Dentistry
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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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