The integrin alphavbeta5 is expressed on avian osteoclast precursors and regulated by retinoic acid.
Osteoclasts arise by proliferation, differentiation, and subsequent fusion of marrow-derived precursors, all processes requiring attachment to matrix. Integrins are important mediators of cell-matrix recognition and bone is rich in proteins containing the Arg-Gly-Asp motif, recognized primarily by alphav integrins. Thus, we determined if avian osteoclast precursors express integrins capable of mediating initial attachment to matrix proteins. Early, marrow-derived osteoclast precursors, when first isolated, contain no detectable alphavbeta3, but express an alphav integrin with an 80 kDa associated beta subunit. Immunoprecipitation with an antibody raised against the conserved beta5 cytoplasmic tail sequence indicates the the alphav associated the integrin is alphavbeta5. Retinoic acid is a resorptive steroid, and its exposure to early osteoclast precursors prompts a time- and dose-dependent decrease in alphavbeta5 expression, while simultaneously stimulating alphavbeta3 expression. Northern analysis reveals that retinoic acid decreases beta5 steady-state mRNA, nontranscriptionally, without altering that of alphav. The finding alphavbeta5 expression decreases under the influence of retinoic acid, an osteoclastogenic steroid, while those of alphavbeta3 rise, suggests that these closely related integrins play separate and complementary roles during osteoclast differentiation.
Sago
K
K
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Teitelbaum
S L
SL
Venstrom
K
K
Reichardt
L F
LF
Ross
F P
FP
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002645:Chickens; D006801:Humans; D016023:Integrins / Q000235:genetics*; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D019030:Receptors, Vitronectin; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
D016023:Integrins; D012333:RNA, Messenger; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D014212:Tretinoin