Inhibition of titanium particle-induced inflammatory osteolysis through inactivation of cannabinoid receptor 2 by AM630.

D C Geng, Y Z Xu, H L Yang, X S Zhu, G M Zhu, X B Wang

Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou 215006, People's Republic of China.

Journal of biomedical materials research. Part A 2010 Oct

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Wear particle could induce inflammatory osteolysis and is the primary pathological factor for aseptic loosening. Although it is known that cannabinoid receptor 2 (CB2) inhibits osteoclast differentiation, the effect on inflammatory osteolysis induced by wear particles remains unclear. This study examined the effect of CB2 in the regulation of osteoclast differentiation in a murine macrophage cell line (RAW264.7), which has been shown to be stimulated by titanium (Ti) particles and receptor activator of the NF-kappaB ligand (RANKL). Results showed that CB2 expression in RAW cells cultured with Ti particles and RANKL. CB2 inactivation by AM630, a CB2 selective antagonist, effectively inhibited osteoclastogenesis in the differentiation medium system. AM630 treatment (> or =100 nM) significantly reduced the number of tartrate-resistant acid phosphatase-positive cells when compared with the control. Real-time reverse transcription polymerase chain reaction analysis revealed that AM630 (100 nM) inhibited mRNA expression of RANK and cathepsin K in RAW cells stimulated by Ti particles and RANKL. Moreover, enzyme-linked immunosorbent assay showed that AM630 (100 nM) reduced protein expression of interleukin-1beta and tumor necrosis factor-alpha in RAW cells cultured with Ti particles. In addition, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide revealed that AM630 had no toxic effect on RAW cells. These results suggested that CB2 inactivation by AM630 could provide a promising therapeutic target for treating or preventing aseptic loosening. Copyright 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

Citation

D C Geng, Y Z Xu, H L Yang, X S Zhu, G M Zhu, X B Wang. Inhibition of titanium particle-induced inflammatory osteolysis through inactivation of cannabinoid receptor 2 by AM630. Journal of biomedical materials research. Part A. 2010 Oct;95(1):321-6