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Bone sialoprotein (BSP) is a protein thought to be highly specific for bone. BSP contains an arginine-glycine-aspartic acid (RGD) cell attachment sequence involved in osteoclast adhesion to bone matrix via the vitronectin receptor and plays an important role in the early process of bone mineralization and resorption. The study by Bellahcene et al1 in this issue of Circulation Research indicates that BSP mediates adhesion and chemotactic migration of endothelial cells and promotes angiogenesis, suggesting that BSP may be an important factor in angiogenesis and the initiation of atherosclerosis, two processes that are probably related.In earlier studies, Folkman2 hypothesized that tumor growth beyond a few millimeters requires recruitment and growth of a new microcirculation, or angiogenesis, which is induced by tumors as lifelines for oxygen and nutrients. New blood vessels also provide exits for cancer cells to spread to other parts of the body. Angiogenesis is also involved in physiological conditions, such as embryogenesis, and other pathological conditions, such as wound healing. The process of angiogenesis requires a highly coordinated series of events, including endothelial cell proliferation, migration, tube and lumen formation, and, in some cases, recruitment of smooth muscle cells (SMCs) and other adventitial cells.Adhesive interaction of cells with components of the extracellular matrix is a recognized requirement for cell proliferation and migration. Evidence indicates that many of the adhesive interactions are mediated by members of the integrin family of heterodimeric adhesion receptors. Among these integrins, αvβ3, which is expressed by a variety of cell types, has been shown to play a key role in the cell migration involved in metastasis and angiogenesis.3 The work presented by Bellahcene et …

Bone Sialoprotein and the Paradox of Angiogenesis Versus Atherosclerosis