A role for alphaV integrin subunit in TGF-beta-stimulated osteoclastogenesis.
TGF-beta increases bone resorption in vivo and greatly increases osteoclast formation stimulated by receptor activator of NF-kappaB ligand (RANKL) in vitro. TGF-beta does not independently affect the differentiation state of RAW264.7 preosteoclasts, but increases cell attachment to vitronectin. This effect is mediated by increased expression of alphaV integrin subunit mRNA and protein. Concomitant with induction of osteoclast differentiation, RANKL causes relocation of alphaV to focal sites in the cell. This effect is potentiated by TGF-beta. Integrin blockade disrupts both attachment to vitronectin and RANKL-induced osteoclast formation, but culture on vitronectin has little effect. Ectopic expression of alphaV stimulates multinucleation of RAW264.7 cells and increases the number of osteoclasts formed in the presence of RANKL. These data suggest that TGF-beta potentiates RANKL-induced osteoclast formation, in part by increased expression of the alphaV integrin subunit, which may contribute to cell fusion.
Chin
Synn Lynn
SL
University of Melbourne, Department of Medicine, St. Vincent's Hospital, 4th Floor Clinical Sciences Building, 3065 Fitzroy, Vic, Australia.
Johnson
Sandra A
SA
Quinn
Julian
J
Mirosavljevic
Danijela
D
Price
John T
JT
Dudley
Andrew C
AC
Thomas
David M
DM
D000818:Animals; D002448:Cell Adhesion; D016923:Cell Death; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005109:Extracellular Matrix / Q000502:physiology; D039564:Integrin alphaV / Q000235:genetics / Q000502:physiology*; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016023:Integrins / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology* / Q000648:ultrastructure; D021122:Protein Subunits; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D039564:Integrin alphaV; D039302:Integrin alphaVbeta3; D016023:Integrins; D021122:Protein Subunits; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1