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.
Chiba
M
M
Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110, USA.
Teitelbaum
S L
SL
Cao
X
X
Ross
F P
FP
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