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. 2009 Dec;3(3-4):311-22.
doi: 10.1007/s12079-009-0068-0. Epub 2009 Oct 2.

The role of osteopontin in inflammatory processes

Susan Amanda Lund  1 , Cecilia M Giachelli, Marta Scatena
Affiliations

The role of osteopontin in inflammatory processes

Susan Amanda Lund et al. J Cell Commun Signal. 2009 Dec.

Abstract

Osteopontin (OPN) is a matricellular protein that mediates diverse biological functions. OPN is involved in normal physiological processes and is implicated in the pathogenesis of a variety of disease states, including atherosclerosis, glomerulonephritis, cancer, and several chronic inflammatory diseases. Through interactions with several integrins, OPN mediates cell migration, adhesion, and survival in many cell types. OPN also functions as a Th1 cytokine, promotes cell-mediated immune responses, and plays a role in chronic inflammatory and autoimmune diseases. Besides its function in inflammation, OPN is also a regulator of biomineralization and a potent inhibitor of vascular calcification.

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Figures

Fig. 1
Fig. 1
OPN structural features. The cell adhesive domains are indicated in color. The known specific integrin receptors for each adhesion domain are also shown in color. The calcium (Ca2+) binding domains are shown in yellow and other matrix binding domains are in black. Also shown are known phosphorylation sites (P). Arrows indicate known cleavage sites for thrombin and MMPs. Thrombin cleavage site in blue and MMPs cleavage site in green
Fig. 2
Fig. 2
OPN regulation of immune and inflammatory cells. OPN is secreted and modulates the function of macrophages, DCs and T Cells. OPN may induce macrophage accumulation by promoting migration and survival. Further, OPN induces IL-12 and inhibits IL-10 in macrophages, thus, propagating a Th1 response. In DCs OPN appears to modulate their function as an extracellular soluble cytokine and also as an intracellular molecule (iOPN). Both OPN forms appear to induce Th1 polarization. Extracellular OPN appears to induce expression of IL-12 and TNF-α, and iOPN appears to regulate the production of INF-α. In T cells OPN induces migration, proliferation, survival, and IL-17 secretion. These two latter functions have been correlated with Th17 responses and autoimmunity. Further, OPN appears to induce IFN-γ secretion by T cells thus propagating a Th1 response. Finally, the N-terminal OPN fragment (containing the activated adhesive domain SVVYGLR) may be important in the propagation of rheumatoid arthritis
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References

    1. Agnholt J, Kelsen J, Schack L, Hvas CL, Dahlerup JF, Sorensen ES. Osteopontin, a protein with cytokine-like properties, is associated with inflammation in Crohn’s disease. Scand J Immunol. 2007;65(5):453–460. - PubMed
    1. Agnihotri R, Crawford HC, Haro H, Matrisian LM, Havrda MC, Liaw L. Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin) J Biol Chem. 2001;276(30):28261–28267. - PubMed
    1. Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S, Rittling SR, Denhardt DT, Glimcher MJ, Cantor H. Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science. 2000;287(5454):860–864. - PubMed
    1. Bayless KJ, Davis GE. Identification of dual alpha4 beta1 integrin binding sites within a 38 amino acid domain in the N-terminal thrombin fragment of human osteopontin. J Biol Chem. 2001;276(16):13483–13489. - PubMed
    1. Bellahcene A, Castronovo V, Ogbureke KU, Fisher LW, Fedarko NS. Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer. Nat Rev Cancer. 2008;8(3):212–226. - PMC - PubMed