Binding of osteopontin to the osteoclast integrin alpha v beta 3.
Occupancy of the chicken osteoclast alpha v beta 3 integrin stimulates immediate cell signals. Peptides from osteopontin containing Arg-Gly-Asp 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 LM609, a monoclonal antibody to the alpha v beta 3 integrin. 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 was due to activation of a plasma membrane Ca(2+)-ATPase. Thus, the data suggest that ligand binding to the osteoclast alpha v beta 3 integrin results in a reduction in cytosolic Ca2+ which participates in regulation of osteoclast function.
Miyauchi
A
A
Department of Medicine, Jewish Hospital, Washington University Medical Center, St Louis, Missouri.
Alvarez
J
J
Greenfield
E M
EM
Teti
A
A
Grano
M
M
Colucci
S
S
Zambonin-Zallone
A
A
Ross
F P
FP
Teitelbaum
S L
SL
Cheresh
D
D
D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology; D001842:Bone and Bones / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D058574:Integrin-Binding Sialoprotein; D016023:Integrins / Q000378:metabolism*; D009994:Osmolar Concentration; D010010:Osteoclasts / Q000378:metabolism*; D053495:Osteopontin; D010455:Peptides / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000378:metabolism* / Q000494:pharmacology
D058574:Integrin-Binding Sialoprotein; D016023:Integrins; D010455:Peptides; D012795:Sialoglycoproteins; D053495:Osteopontin; D002118:Calcium