ACY-1215 exhibits anti-inflammatory and chondroprotective effects in human osteoarthritis chondrocytes via inhibition of STAT3 and NF-kappa B signaling pathways

Cheng, C; Shan, WS; Huang, W; Ding, ZF; Cui, GJ; Liu, F; Lu, W; Xu, JG; He, W; Yin, ZS

Yin, ZS (reprint author), Anhui Med Univ, Affiliated Hosp 4, Dept Orthopaed, 372 Tun Xi Rd, Hefei 230032, Anhui, Peoples R China.; He, W (reprint author), Anhui Med Univ, Sch Basic Med Sci, 81 Mei Shan Rd, Hefei 230032, Anhui, Peoples R China.



Cartilage degeneration is a basic pathological feature of osteoarthritis (OA), and there is growing evidence that it is associated with inflammation. ACY-1215, a selective HDAC6 inhibitor, has been reported to have anti-inflammatory effects. Here, we investigated the anti-inflammatory and chondroprotective effects of ACY-1215 in IL-1 beta-stimulated human primary chondrocytes and C28/I2 cells. The results suggested that ACY-1215 can markedly suppress the expression of inflammatory factors, including IL-1 beta and IL-6 in human primary chondrocytes and C28/I2 cells. Furthermore, ACY-1215 exerts potent chondroprotection through the amelioration of cartilage degradation by inhibiting the expression of matrix-degrading proteases, including MMP-1 and MMP-13 in chondrocytes. These effects may be related to ACY-1215 induced down-regulation of NF-kappa B and STAT3 pathways in OA chondrocytes. Taken together, our results show that ACY-1215 may be a potential and promising therapeutic drug for the management of OA.

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