Transcriptional induction of cyclooxygenase-2 in osteoclast precursors is involved in RANKL-induced osteoclastogenesis.

Regulation of osteoclast differentiation is key to understanding the pathogenesis and to developing treatments for bone diseases such as osteoporosis. To gain insight into the mechanism of the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-specific induction of the osteoclast differentiation program, we took a suppression-subtractive hybridization screening approach to identify genes specifically induced via the RANKL-Rac1 signaling pathway. Among identified targets, we show that RANKL selectively induces cyclooxygenase (COX) 2 expression via Rac1 that results in turn in production of prostaglandin E2 (PGE2) in RAW 264.