Retinoic acid stimulates expression of the functional osteoclast integrin α(v)β₃: Transcriptional activation of the β₃ but not the α(v) gene

The capacity of osteoclasts to resorb bone depends, in part, on the surface expression of the integrin α(v)β₃. We have investigated whether the steroid hormone retinoic acid, known to stimulate bone resorption, regulates the appearance of the α(v)β₃ complex in avian osteoclast presursors. Using surface labeling, followed by immunoprecipitation with a α(v)β₃-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 α(v) mRNA do not change, while those for β₃ rise significantly from their initially low levels. Nuclear run-on studies confirm that steroid treatment stimulates transcription of the β₃ but not the α(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.