J. Cell Commun. Signal. (2009) 3:311–322 DOI 10.1007/s12079-009-0068-0 RESEARCH ARTICLE The role of osteopontin in inflammatory processes Susan Amanda Lund & Cecilia M. Giachelli & Marta Scatena Received: 15 May 2009 / Accepted: 9 September 2009 / Published online: 2 October 2009 # The Author(s) 2009. This article is published with open access at Springerlink.com 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. Keywords Inflammation . Matricellular protein . Osteopontin Abbreviations DC Dendritic cell IFN Interferon MMP Matrix metalloproteinase OPN Osteopontin PBMCs Peripheral blood mononuclear cells Introduction OPN is a secreted phosphorylated glycoprotein that mediates diverse biological functions. Originally isolated S. A. Lund : C. M. Giachelli : M. Scatena (*) Department of Bioengineering, University of Washington, Box 358056, Seattle, WA 98195, USA e-mail: mscatena@u.washington.edu from bone, OPN was later shown to have a wider distribution (Brown et al. 1992). In adults, OPN expression is normally limited to the bone, kidney, and epithelial linings, and is secreted in bodily fluids including milk, blood and urine (Chen et al. 1993). In contrast to its restricted distribution in normal tissue, OPN is strikingly upregulated at sites of inflammation and tissue remodeling (Liaw et al. 1998; O’Brien et al. 1994). OPN exists both as a component of the extracellular matrix and as a soluble cytokine. Physiologically OPN is thought to regulate biomineralization in bone tissue, and to reduce growth and aggregation of calcium crystals in epithelial tissues (Wesson et al. 2003). OPN has also been implicated in a variety of disease states, where it mediates diverse cellular functions such as adhesion, migration, and survival of several different cell types, including regulating and propagating inflammatory responses of macrophages, T- cells, and dendritic cells. The pleiotropic nature of OPN may reflect the various isoforms, post-translational mod- ifications, and diversity of cell types which OPN can interact with. Clinically, OPN plasma levels are correlated with chronic inflammatory diseases such as Crohn’s disease (Agnholt et al. 2007), cancer (El-Tanani et al. 2006), atherosclerosis, aortic abdominal aneurysms (Golledge et al. 2007), and autoimmune diseases including lupus (Kariuki et al. 2009), multiple sclerosis (Comabella et al. 2005), and rheumatoid arthritis (Sennels et al. 2008). In this review we will focus on the role of OPN in inflammation biology. OPN structure OPN was originally isolated from bone and was later independently identified as secreted phosphoprotein I