1 alpha,25-dihydroxyvitamin D3 up-regulates expression of the osteoclast integrin alpha v beta 3.
Osteoclast precursors selectively attach to bone and differentiate into multinucleated cells that function to remodel and resorb it. We have shown previously that attachment of osteoclasts to bone and subsequent resorption are mediated by the integrin alpha v beta 3. 1 alpha,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) enhances osteoclast precursor differentiation in vivo by mechanisms that are still not clearly understood but entail enhanced attachment of cells to bone. This observation raises the possibility that at least one component of vitamin D-induced osteoclast precursor differentiation involves modulation of integrin expression. To test if the steroid modulates the osteoclast integrin alpha v beta 3 (the vitronectin receptor), we examined the effects of 1,25-(OH)2D3 on transcription of the alpha v gene as well as surface expression and function of alpha v beta 3, in chicken osteoclast precursors. Treatment of the cells with 1,25-(OH)2D3 led to a progressive dose-dependent increase in steady state alpha v mRNA levels with enhanced expression evident within 24 h. The effect was receptor-mediated as indicated by the effects of other vitamin D analogs. The increase in alpha v mRNA levels did not reflect decreased message degradation but, as demonstrated by nuclear run-on experiments, was due to accelerated rates of transcription. Most importantly, induction of alpha v mRNA by 1,25-(OH)2D3 was mirrored by higher levels of expression of alpha v beta 3 on the cell surface, as well enhanced attachment to its substrate, vitronectin.
Medhora
M M
MM
Renal Division, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
Teitelbaum
S
S
Chappel
J
J
Alvarez
J
J
Mimura
H
H
Ross
F P
FP
Hruska
K
K
D000818:Animals; D015152:Blotting, Northern; D002117:Calcitriol / Q000494:pharmacology*; D002448:Cell Adhesion / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D002478:Cells, Cultured; D002645:Chickens; D003609:Dactinomycin / Q000494:pharmacology; D016023:Integrins / Q000096:biosynthesis* / Q000235:genetics; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
D016023:Integrins; D012333:RNA, Messenger; D003609:Dactinomycin; D012313:RNA; D002117:Calcitriol