Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption

• Published in: The Journal of biological chemistry 1993-05, Vol.268 (13), p.9901-9907
• Main Authors: Ross, F P, Chappel, J, Alvarez, J I, Sander, D, Butler, W T, Farach-Carson, M C, Mintz, K A, Robey, P G, Teitelbaum, S L, Cheresh, D A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Bone Matrix - physiology; Bone Resorption - physiopathology; Cell Adhesion; Humans; Integrin-Binding Sialoprotein; Integrins - metabolism; Kinetics; Models, Biological; Molecular Sequence Data; Oligopeptides - metabolism; Osteoclasts - metabolism; Osteoclasts - physiology; Osteopontin; Rats; Sialoglycoproteins - metabolism; Space life sciences
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)98430-9

We have investigated the mechanism by which osteoclasts adhere to and resorb bone. We show that these cells express beta 1 and beta 3 integrins which are involved in attachment to purified bone matrix proteins. Binding to osteopontin and bone sialoprotein is mediated by alpha v beta 3, while a beta 1 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 alpha v beta 3 complex but not by an antibody against beta 1 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 alpha v beta 3. Moreover, collagen, which constitutes 90% of its organic matrix, is minimally involved in binding of chicken osteoclasts to bone.