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Background
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Osteopontin (OPN), also known as early T lymphocyte activation 1 (Eta-1), is a secreted multifunctional glyco-phosphoprotein with roles in bone metabolism, immune regulation, tissue remodeling , cell survival, and tumor progression . Gene structure and chromosomal location identify OPN as a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family that also includes bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein(DSPP), enamelin (ENAM), and matrix extracellular phosphoglycoprotein (MEPE). Murine OPN issynthesized as a 294 amino acid (aa) precursor protein with a predicted 16 aa signal peptide and a highly unusual mature protein sequence, containing 68 acidic aa and 23 potential Ser/Thr phosphorylation sites. Although the predicted molecular weight of OPN is 31 kDa,phosphorylation and N- and O-glycosylation may allow it to appear as large as 75 kDa. Variability in post-translational modifications can influence the activity of OPN. Osteopontin, as indicated by its name meaning “bone bridging”, is highly expressed in mineralized tissues. It is also expressed in other tissues including cartilage, kidney, vascular tissues, activated macrophages, lymphocytes, and epithelia. A portion of cell expressed OPN is also retained intracellularly. In vitro, OPN stimulates the adhesion of osteoclasts to bone, and bone resorption is blocked by inhibition of this interaction. Knockout mice have outwardly normal bone development, but exhibit deficient postnatal bone resorption in several contexts, supporting a role for OPN in osteoclast function. In kidney epithelia, OPN is upregulated by high concentrations of oxalate and inhibits calcium oxalate crystal nucleation and growth. In endothelial and smooth muscle cells, OPN is upregulated by high phosphate concentration and during atherosclerosis, binding of OPN to hydroxyapatite inhibits calcification of blood vessels and heart valves. OPN expression by macrophages and T cells is upregulated by inflammatory mediators including LPS,NO, IL-1β, and TNF-α. OPN regulates macrophage differentiation and recruitment. It also functions as a chemotactic factor and co-stimulator of T cells and may act as a Th1 cytokine, stimulating IL-12 production. OPN production by macrophages is upregulated at sites of tissue remodeling including the placenta, endometrium and myocardium post-infarction. OPN is expressed by many tumor types and plays a role in tumor progression and metastasis. OPN may also be upregulated during autoimmune processes such as rheumatoid arthritis or in 2 granulomatous lesions in response to infections such as tuberculosis.
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