Bone and Tooth Matrix Biochemistry and Metabolism

Fisher, L W.

Abstract

The extracellular matrix proteins of the bones and teeth are key elements in the structure and metabolism of these tissues. The goal of this project is to study matrix proteins specific to each mineralizing skeletal tissue in order to understand their molecular structure and biological function. Analytical procedures (polyacrylamide gel electrophoresis, immunoblotting, specific; dye-binging, RIA, ELISA, etc.) have been developed to quantitate the levels of noncollagenous proteins in bone including osteonectin, bone sialoprotein, osteopontin, bone proteoglycans BGN and DCN, dentin phosphophoryn and the N- propeptide and C-propeptide of type 1(I) collagen in (a) surgical specimens of bony tissue and (b) serum (osteonectin). Changes in the noncollagenous protein profile with age and variety of bone (and tooth) diseases have been observed in man and several animal models. We have been highly successful at producing antisera against, synthetic peptides for all of the human bone noncollagenous proteins. These antisera have proven useful in immuno precipitation studies, immunolocalization,l immunodetection and on Western blots. We have successfully cloned and sequence human bone proteoglycans I (biglycan) and II (decorin), sialoprotein (BSP) and two members of the osteopontin family (OPN-L and OPN-2). The human biglycan gene ha$ been cloned and sequenced.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Dental & Craniofacial Research (NIDCR)
• Type: Intramural Research (Z01)
• Project #: 1Z01DE000074-18
• Application #: 3875177
• Support Year: 18
• Fiscal Year: 1990

Institution

• Name: National Institute of Dental & Craniofacial Research
• Country: United States

Publications

von Marschall, Zofia; Fisher, Larry W (2010) Dentin sialophosphoprotein (DSPP) is cleaved into its two natural dentin matrix products by three isoforms of bone morphogenetic protein-1 (BMP1). Matrix Biol 29:295-303

Bellahcene, Akeila; Castronovo, Vincent; Ogbureke, Kalu U E et al. (2008) Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer. Nat Rev Cancer 8:212-26

Jain, Alka; Fisher, Larry W; Fedarko, Neal S (2008) Bone sialoprotein binding to matrix metalloproteinase-2 alters enzyme inhibition kinetics. Biochemistry 47:5986-95

Inkson, Colette A; Ono, Mitsuaki; Kuznetsov, Sergei A et al. (2008) TGF-beta1 and WISP-1/CCN-4 can regulate each other's activity to cooperatively control osteoblast function. J Cell Biochem 104:1865-78

Adams, J; Fantner, G E; Fisher, L W et al. (2008) Molecular energy dissipation in nanoscale networks of Dentin Matrix Protein 1 is strongly dependent on ion valence. Nanotechnology 19:384008

Ogbureke, Kalu U E; Fisher, Larry W (2007) SIBLING expression patterns in duct epithelia reflect the degree of metabolic activity. J Histochem Cytochem 55:403-9

de Vega, Susana; Iwamoto, Tsutomu; Nakamura, Takashi et al. (2007) TM14 is a new member of the fibulin family (fibulin-7) that interacts with extracellular matrix molecules and is active for cell binding. J Biol Chem 282:30878-88

Ogbureke, Kalu U E; Nikitakis, Nikolaos G; Warburton, Gary et al. (2007) Up-regulation of SIBLING proteins and correlation with cognate MMP expression in oral cancer. Oral Oncol 43:920-32

Fantner, Georg E; Adams, Jonathan; Turner, Patricia et al. (2007) Nanoscale ion mediated networks in bone: osteopontin can repeatedly dissipate large amounts of energy. Nano Lett 7:2491-8

Nam, Jeong-Seok; Suchar, Adam M; Kang, Mi-Jin et al. (2006) Bone sialoprotein mediates the tumor cell-targeted prometastatic activity of transforming growth factor beta in a mouse model of breast cancer. Cancer Res 66:6327-35