Inhibition of titanium particle-induced inflammatory osteolysis through inactivation of cannabinoid receptor 2 by AM630
✍ Scribed by D. C. Geng; Y. Z. Xu; H. L. Yang; X. S. Zhu; G. M. Zhu; X. B. Wang
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 552 KB
- Volume
- 95A
- Category
- Article
- ISSN
- 1549-3296
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✦ Synopsis
Abstract
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‐κB 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 (≥100 n__M__) 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 n__M__) 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 n__M__) reduced protein expression of interleukin‐1β and tumor necrosis factor‐α 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. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.