Abstract：Objective To observe the effect of selective cyclooxygenase-2 (COX-2) inhibitor parecoxib in treatment of titanium-particle-induced inflammatory osteolysis and examine the relationship between COX-2 and receptor activator of NF-κB ligand (RANKL)/ receptor activator of NF-κB (RANK) signaling pathway. Methods Fifteen out of 45 female BALB/c mice were served as skull donators. The rest were divided into blank group, control group, and treatment group according to random number table, with 10 mice per group. Models of osteolysis in mice induced by titanium particles were established. Treatment group were given parecoxib (6 mg·kg-1·d-1) at 2 days prior to the modeling, which was continued tilled two weeks after the modeling. Mature osteoclasts were identified using tartrate-resistant acid phosphatase (TRAP) staining. Expressions of COX-2 and RANKL were detected using immunohistochemical staining. Levels of dinoprostone (PGE2), IL-1β, and TNF-a in capsule wall were examined by ELISA method. Expressions of the mRNA for COX-2, IL-1β, TNF-α, RANK and RANKL were determined by quantitative RT-PCR. Results TRAP staining revealed ratio of TRAP positive area to bone graft area was (0.27±0.03)% in treatment group, with statistical difference from control group \[(0.60±0.06)%\] (P< 0.01). Immunohistochemical staining showed COX-2 and RANKL intensive area in capsule wall were increased after titanium particle stimulation. Instead, RANKL positive area was decreased in treatment group, but the decrease of COX-2 was insignificant. RT-PCR showed titanium particles stimulation could enhance the mRNA expressions of COX-2, IL-1β, TNF-α, RANKL, and RANK. Whereas, mRNA expressions of RANK and RANKL in treatment group were reduced, with statistical difference in contrast to control group (P< 0.01). ELISA showed PGE2 level was (202.62±11.49) pg/ml in treatment group, with statistical difference from control group\[(407.60±13.55) pg/ml\] (P<0.01). Levels of IL-1β and TNF-α had no statistical differences between treatment group and control group (P>0.05). Conclusions Selective COX-2 inhibitor parecoxib impedes expression of RANK/RANKL, reduces the number of TRAP positive osteoclasts, and thereafter ameliorates osteolysis. Whereas, parecoxib presents no significant influence on expressions of COX2, TNF-α, and IL-1β.
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