Retinoic acid stimulates expression of the functional osteoclast integrin alpha v beta 3: transcriptional activation of the beta 3 but not the alpha v gene.
The capacity of osteoclasts to resorb bone depends, in part, on the surface expression of the integrin alpha v beta 3. We have investigated whether the steroid hormone retinoic acid, known to stimulate bone resorption, regulates the appearance of the alpha v beta 3 complex in avian osteoclast presursors. Using surface labeling, followed by immunoprecipitation with a alpha v beta 3-specific antibody, we show that retinoic acid increases surface expression of the heterodimer in a dose- and time-dependent manner. Northern analysis reveals that the high basal steady-state levels of alpha v mRNA do not change, while those for beta 3 rise significantly from their initially low levels. Nuclear run-on studies confirm that steroid treatment stimulates transcription of the beta 3, but not the alpha v gene. Osteoclast precursors treated with retinoic acid exhibit increased multinucleation and expression of the osteoclast marker enzyme tartrate-resistant acid phosphatase. However, the fused cells do not have an increased capacity to resorb bone. In summary, multinucleated cells generated in this study do not represent fully differentiated bone-resorbing polykaryons. These results suggest that treatment of osteoclast precursors with retinoic acid is necessary, but insufficient, for expression of the mature osteoclast phenotype.
Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110, USA.
M
M
Chiba
S L
SL
Teitelbaum
X
X
Cao
F P
FP
Ross
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001426:Bacterial Proteins; D002117:Calcitriol / Q000494:pharmacology; D002642:Chick Embryo; D039661:Integrin beta3; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
D015703:Antigens, CD; D001426:Bacterial Proteins; D039661:Integrin beta3; C079092:MtrB protein, Bacteria; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D019030:Receptors, Vitronectin; D014157:Transcription Factors; D014212:Tretinoin; D002117:Calcitriol