Wear particles enhance autophagy through up-regulation of CD147 to promote osteoclastogenesis

磨损颗粒通过上调 CD147 来增强自噬,从而促进破骨细胞生成

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作者:Baohua Su, Deng Li, Jie Xu, Yingbin Zhang, Zhiqing Cai, Max Daniel Kauther, Ruofan Ma

Conclusion

Our findings suggested a possible mechanism underlying wear debris-induced osteolysis and identified CD147 as a potential therapeutic target in aseptic loosening.

Methods

Effects of titanium particles on CD147 and RANKL mRNA were detected by QPCR; protein level of CD147 and Beclin-1 were detected by Western blot; soluble RANKL were detected by ELISA. To determine the effect of CD147 and autophagy, KG-1a cells were transfected with siRNA-CD147 or treated with autophagy inhibitor CQ (chloroquine), and then co-cultured with different sizes of titanium particles.

Results

Our results showed that 0.2-1.2 µm and 1.2-10 µm titanium particles up-regulate CD147 to activate autophagy, which increase the level of soluble RANKL to promote osteoclastogenesis. Suppression of CD147 with siRNA could diminish particle-induced autophagy and soluble RANKL expression. In addition, CQ could dramatically reduce particle-induced soluble RANKL expression.

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