The effect of selective cyclooxygenase-2 inhibitor on human osteoclast precursors to influence osteoclastogenesis in vitro

The inducible prostaglandin synthesis enzyme, cyclooxygenase-2 (COX-2), is involved in bone resorption and osteoclastogenesis, and acts indirectly through prostaglandin E2 (PG E2) produced by osteoblastic cells. This study was undertaken to investigate whether celecoxib (a selective COX-2 inhibitor) has a direct effect on human osteoclast precursors to influence osteoclastogenesis in vitro. Human peripheral blood mononuclear cells (PBMCs) were cultured on glass coverslips and dentine slices with soluble receptor activator of NF-kB ligand (sRANKL) and macrophage colony stimulating factor (M-CSF). COX inhibitors including celecoxib were added to the cultures. Osteoclast formation was assessed as the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), and the functional evidence of lacunar resorption pits on dentine slices was assessed. Celecoxib and indomethacin inhibited osteoclast formation and the extent of lacunar resorption in a dose-dependent manner, but the effect of indomethacin was less than that of celecoxib. Mofezolac affected neither the number of TRAP-positive MNCs nor the extent of lacunar resorption pits. These results indicate that celecoxib influences not only osteoclast formation through osteoblastic cells but also acts directly on circulating osteoclast precursors to influence human osteoclast differentiation. The effect of celecoxib on osteoclast precursors may be related to the COX-2 signal pathway.