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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR044434-01
Application #
2006870
Study Section
General Medicine B Study Section (GMB)
Project Start
1996-12-15
Project End
2000-11-30
Budget Start
1996-12-15
Budget End
1997-11-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Rutgers University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
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
Ishijima, Muneaki; Ezura, Yoichi; Tsuji, Kunikazu et al. (2006) Osteopontin is associated with nuclear factor kappaB gene expression during tail-suspension-induced bone loss. Exp Cell Res 312:3075-83
Shapses, S A; Cifuentes, M; Spevak, L et al. (2003) Osteopontin facilitates bone resorption, decreasing bone mineral crystallinity and content during calcium deficiency. Calcif Tissue Int 73:86-92
Chellaiah, Meenakshi A; Biswas, Rajat S; Rittling, Susan R et al. (2003) Rho-dependent Rho kinase activation increases CD44 surface expression and bone resorption in osteoclasts. J Biol Chem 278:29086-97
Hampel, Dierk J; Sansome, Christine; Romanov, Victor I et al. (2003) Osteopontin traffic in hypoxic renal epithelial cells. Nephron Exp Nephrol 94:e66-76
Denhardt, David T; Mistretta, Devra; Chambers, Ann F et al. (2003) Transcriptional regulation of osteopontin and the metastatic phenotype: evidence for a Ras-activated enhancer in the human OPN promoter. Clin Exp Metastasis 20:77-84
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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