Osteopontin

Abstract

Osteopontin is an arginine-glycine–aspartate (RGD) containing adhesive glycoprotein first identified in bone but subsequently detected in many other tissues, including, dentin, cartilage, kidney, and vascular tissues.1–3 It is expressed by a wide variety of inflammatory cells (eg, macrophages, T lymphocytes, NK cells), and, to a lesser extent, by endothelial cells and smooth muscle cells. The RGD domain facilitates tissue binding of osteopontin to various extracellular matrix proteins, such as αvβ3 integrin and fibronectin. Additionally, osteopontin may engage CD44 through an RGD-independent mechanism. In extracellular fluids, osteopontin functions as a cytokine, and its plasma levels are increased in autoimmune diseases such as lupus, rheumatoid arthritis, and multiple sclerosis.4 The diverse biological actions of osteopontin could potentially regulate many processes pertinent to vascular disease, including inflammation, cell adhesion, viability, angiogenesis, and calcification (Figure).5,6 Such actions may underlie its presumed role in the pathophysiology of atherosclerosis and in modulating arteriopathy associated with diabetes and chronic renal failure (reviewed by Johnson et al7). Of relevance to the present topic, Bruemmer et al reported that deletion of osteopontin reduced formation of abdominal aortic aneurysms (AAA) in mice infused with angiotensin II.8 Overview of potential mechanisms whereby osteopontin may bind to extracellular matrix proteins (eg, integrin) and adhesion molecules (eg, CD44) to regulate vascular disease. See page 655 Conceptually, it is logical to presume that osteopontin would contribute to the pathogenesis of AAA. First, in experimental models and in humans, AAA are characterized by extensive inflammatory cell infiltration and induction of proinflammatory cytokines.9–12 Osteopontin can positively regulate these processes through several mechanisms. Second, the inflammatory milieu of AAA is associated …