The extracellular matrices of bones and teeth that give these unique tissues their shape and strength are synthesized and maintained throughout life by highly specialized cells. The cells' ability to assemble, mineralize and maintain the matrices is generally thought to be modulated through a variety of noncollagenous proteins (NCP). The goal of this project is to study the structure and function of several of these noncollagenous proteins. We have completed the cloning and sequencing of human and certain useful animal model noncollagenous proteins including bone sialoprotein (BSP), osteopontin (OPN), decorin (DCN), and biglycan (BGN). The human biglycan gene has been sequenced and localized to the end of the long arm of the X chromosome. Comparison of the BGN gene structure to other TGF-~ binding proteins has led us to hypothesize that the TGF-~ binding domain may be in the C-terminal disulfide loop. The human decorin gene has been partially cloned and is much larger than BGN. Its intron-exon junctions, however, appear to be identical to the BGN gene. The DCN gene is located at 12q21.3. We have successfully produced monospecific antisera to all of the major NCP. In collaboration with Dr. Paolo Bianco, we have used both the antisera and cDNA probes to begin studies on the developmental pattern of expression of these proteins in human and rodent models. Production of the mg quantities of nondenatured protein necessary for structure-function studies has been successful for rat BSP. We have conducted physicochemical studies on the purified BSP. Furthermore, we have preliminary evidence for a cryptic cell attachment domain other that the ArgGlyAsp (RGD) tripeptide typical of the integrin-binding class of receptors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000074-19
Application #
3854164
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
1991
Total Cost
Indirect Cost
Name
National Institute of Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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
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
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
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
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
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

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