Recognition of osteopontin and related peptides by an alpha v beta 3 integrin stimulates immediate cell signals in osteoclasts.
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.
Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
A
A
Miyauchi
J
J
Alvarez
E M
EM
Greenfield
A
A
Teti
M
M
Grano
S
S
Colucci
A
A
Zambonin-Zallone
F P
FP
Ross
S L
SL
Teitelbaum
D
D
Cheresh
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002645:Chickens; D058574:Integrin-Binding Sialoprotein; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000378:metabolism*; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism
D058574:Integrin-Binding Sialoprotein; D016023:Integrins; D012795:Sialoglycoproteins; D053495:Osteopontin; D002118:Calcium