Interactions between the bone matrix proteins osteopontin and bone sialoprotein and the osteoclast integrin alpha v beta 3 potentiate bone resorption.
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.
Ross
F P
FP
Department of Pathology and Laboratory Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
Chappel
J
J
Alvarez
J I
JI
Sander
D
D
Butler
W T
WT
Farach-Carson
M C
MC
Mintz
K A
KA
Robey
P G
PG
Teitelbaum
S L
SL
Cheresh
D A
DA
D000595:Amino Acid Sequence; D000818:Animals; D001857:Bone Matrix / Q000502:physiology*; D001862:Bone Resorption / Q000503:physiopathology*; D002448:Cell Adhesion; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D016023:Integrins / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology*; D053495:Osteopontin; D051381:Rats; D012795:Sialoglycoproteins / Q000378:metabolism*
C546871:IBSP protein, human; C546873:Ibsp protein, rat; D058574:Integrin-Binding Sialoprotein; D016023:Integrins; D009842:Oligopeptides; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; C047981:arginyl-glycyl-aspartic acid