Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin α_vβ₃ potentiate bone resorption

We have investigated the mechanism by which osteoclasts adhere to and resorb bone. We show that these cells express β₁ and β₃ integrins which are involved in attachment to purified bone matrix proteins. Binding to osteopontin and bone sialoprotein is mediated by α_vβ₃, while a β₁ integrin is responsible for attachment to fibronectin. Both the rapid attachment by osteoclasts to intact bone particles and their subsequent resorption are blocked by a monoclonal antibody directed to the α_vβ₃ complex but not by an antibody against β₁ integrins. Attachment of osteoclasts to bone is also inhibited with soluble osteopontin, Arg-Gly-Asp-containing peptides derived from both osteopontin and bone sialoprotein, or a monospecific polyclonal antibody against osteopontin. We conclude that both osteoclast adherence to bone and subsequent resorption of its matrix are dependent on interactions between the bone matrix proteins osteopontin and/or bone sialoprotein and the integrin α_vβ₃. Moreover, collagen, which constitutes 90% of its organic matrix, is minimally involved in binding of chicken osteoclasts to bone.