The capacity of osteoclasts to resorb bone depends, in part, on the surface expression of the integrin We have investigated whether the steroid hormone retinoic acid, known to stimulate bone resorption, regulates the appearance of the a,p3 complex in avian osteoclast presursors. Using surface labeling, followed by immunoprecipitation with a a,P,-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 a, mRNA do not change, while those for p3 rise significantly from their initially low levels. Nuclear run-on studies confirm that steroid treatment stimulates transcription of the p3, but not the a, 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. I 1996