Osteopontin (OPN) is a secreted phosphoprotein and acts both as a cytokine and cell adhesion molecule. It can facilitate cell adhesion and initiate a signaling pathway by interacting with cell surface receptors. It binds calcium and suppresses calcium salt precipitation; controls tissue mineralization and bone remodelling; it regulates certain immune functions and has an antiinfectious role; and it can protect cells from oxidant-induced cell damage perhaps by reducing H2O2. It is capable of modulating gene expression and of suppressing the induction of iNOS mRNA synthesis by inflammatory mediators. Nitric oxide is an important second message being implicated in controlling vascular tone, mediating cell killing by certain cytotoxic cells, and conveying signals in nervous system. OPN appears to be the means by which mammalian organisms regulate the production of NO. The purpose of this project is to evaluate the role of osteopontin in various processes mentioned above and how does the OPN carry out its physiological roles. Intricacies of OPN interaction with cell surface receptors and signaling pathways by which OPN alters gene expression are main areas of focus in the proposed research. In addition the role of OPN in protecting the cells from oxidant-induced injury will be investigated.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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General Medicine B Study Section (GMB)
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Sharrock, William J
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Rutgers University
Schools of Arts and Sciences
New Brunswick
United States
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Kazanecki, Christian C; Kowalski, Aaron J; Ding, Tony et al. (2007) Characterization of anti-osteopontin monoclonal antibodies: Binding sensitivity to post-translational modifications. J Cell Biochem 102:925-35
Kazanecki, Christian C; Uzwiak, Dana J; Denhardt, David T (2007) Control of osteopontin signaling and function by post-translational phosphorylation and protein folding. J Cell Biochem 102:912-24
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Chellaiah, M A; Kizer, N; Biswas, R et al. (2003) Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression. Mol Biol Cell 14:173-89
Potter, Melissa R; Rittling, Susan R; Denhardt, David T et al. (2002) Role of osteopontin in murine Lyme arthritis and host defense against Borrelia burgdorferi. Infect Immun 70:1372-81
Yumoto, Kenji; Ishijima, Muneaki; Rittling, Susan R et al. (2002) Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice. Proc Natl Acad Sci U S A 99:4556-61

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