Recognition of osteopontin and related peptides by an alpha v beta 3 integrin stimulates immediate cell signals in osteoclasts |
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Authors: | A Miyauchi J Alvarez E M Greenfield A Teti M Grano S Colucci A Zambonin-Zallone F P Ross S L Teitelbaum D Cheresh |
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Institution: | Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110. |
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Abstract: | We have investigated the nature of immediate cell signals produced by occupancy of the chicken osteoclast alpha v beta 3 integrin. Synthetic osteopontin and peptides from the osteopontin and bone sialoprotein sequences containing Arg-Gly-Asp stimulated immediate reductions in osteoclast cytosolic Ca2+. The changes in cytosolic Ca2+ required the Arg-Gly-Asp sequence and were blocked by a monoclonal antibody to the alpha v beta 3 integrin, LM609. Osteoclast stimulation by the proteins through the integrin did not require immobilization since soluble peptides produced changes in cytosolic Ca2+ and inhibited osteoclast binding to bone particles and bone resorption. The decrease in cytosolic Ca2+ stimulated by osteopontin and related peptides appeared to be due to activation of a plasma membrane Ca(2+)-ATPase by calmodulin. Thus, the data suggest that ligand binding to the osteoclast alpha v beta 3 integrin results in calmodulin-dependent reduction in cytosolic Ca2+ which participates in regulation of osteoclast function. |
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