Cloning and function of rabbit peroxisome proliferator-activated receptor delta/beta in mature osteoclasts

Osteoclasts modulate bone resorption under physiological and pathological c onditions. Previously, we showed that both estrogens and retinoids regulate d osteoclastic bone resorption and postulated that such regulation was dire ctly mediated through their cognate receptors expressed in mature osteoclas ts. In this study, we searched for expression of other members of the nucle ar hormone receptor superfamily in osteoclasts, Using the low stringency ho mologous hybridization method, we isolated the peroxisome proliferator-acti vated receptor delta/beta (PPAR delta/beta) cDNA from mature rabbit osteocl asts. Northern blot analysis showed that PPAR delta/beta mRNA was highly ex pressed in highly enriched rabbit osteoclasts. Carbaprostacyclin, a prostac yclin analogue known to be a ligand for PPAR delta/beta, significantly indu ced both bone-resorbing activities of isolated mature rabbit osteoclasts an d mRNA expression of the cathepsin K, carbonic anhydrase type II, and tartr ate-resistant acid phosphatase genes in these cells. Moreover, the carbapro stacyclin-induced bone resorption was completely blocked by an antisense ph osphothiorate oligodeoxynucleotide of PPAR delta/beta but not by the sense phosphothiorate oligodeoxynucleotide of the same DNA sequence. Our results suggest that PPAR delta/beta may be involved in direct modulation of osteoc lastic bone resorption.