title: Protection against titanium particle-induced osteoclastogenesis by cyclooxygenase-2 selective inhibitor.
abstract: Wear particle-induced osteoclastogenesis is the most common cause of aseptic loosening in total joint arthroplasty. Although cyclooxygenase (COX)-2, an inducible regulator of prostaglandin E2 (PGE2) synthesis, is known to be involved in osteoclast differentiation, its effect on osteoclastogenesis in response to wear particles remains unclear. In this study, we investigated the role of COX-2 in the regulation of osteoclast differentiation in the osteoclast precursor cell line RAW264.7 stimulated with titanium (Ti) particles. The results showed COX-2 expression in the early stages of RAW264.7 differentiation when stimulated with receptor activator of nuclear factor kappa B ligand (RANKL) and Ti particles. Blockade of COX-2 by celecoxib, a COX-2 selective inhibitor, effectively reduced the expression of PGE2 and inhibited differentiation of RAW264.7 cells into tartrate-resistant acid phosphatase-positive (TRAP+) osteoclastic cells. Quantitative real-time polymerase chain reaction revealed that celecoxib inhibited mRNA expression of RANK, cathepsin K (CPK), TRAP, and the nuclear factor of activated T cells c1 (NFATc1) in RAW264.7 cells stimulated by Ti particles and RANKL. Moreover, exogenous PGE2 reversed the inhibitory effects of celecoxib. These results provide direct evidence that COX-2 dependent PGE2 induced by RANKL and Ti particles is required for osteoclastogenesis and suggests that reduced production of PGE2 by inactivation of COX-2 would provide a promising therapeutic target for the treatment of osteoclastogenesis induced by wear particles.
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Road, Suzhou, Jiangsu 215006, People's Republic of China.
authors.forename: D C
authors.initials: DC
authors.lastname: Geng
authors.forename: X S
authors.initials: XS
authors.lastname: Zhu
authors.forename: H Q
authors.initials: HQ
authors.lastname: Mao
authors.forename: B
authors.initials: B
authors.lastname: Meng
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: H L
authors.initials: HL
authors.lastname: Yang
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Xu
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism; D000068579:Celecoxib; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D011475:Prosthesis Failure; D011720:Pyrazoles / Q000494:pharmacology; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase; D014025:Titanium / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D053246:Receptor Activator of Nuclear Factor-kappa B; D013449:Sulfonamides; D014025:Titanium; D051546:Cyclooxygenase 2; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; D000068579:Celecoxib; D015232:Dinoprostone