Department of Orthopaedics, The Fourth Affiliated Hospital of Anhui Medical University, 372#Tun Xi Road, Hefei, 230032, Anhui, China.
Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, 218#Ji Xi Road, Hefei, 230032, Anhui, China.
Biomed Pharmacother. 2019 Jan;109:2464-2471. doi: 10.1016/j.biopha.2018.11.017. Epub 2018 Dec 1.
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-1β-stimulated human primary chondrocytes and C28/I2 cells. The results suggested that ACY-1215 can markedly suppress the expression of inflammatory factors, including IL-1β 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-κB 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.
软骨退变是骨关节炎（OA）的基本病理特征，越来越多的证据表明其与炎症有关。ACY-1215 是一种选择性 HDAC6 抑制剂，具有抗炎作用。在这里，我们研究了 ACY-1215 在 IL-1β刺激的人原代软骨细胞和 C28/I2 细胞中的抗炎和软骨保护作用。结果表明，ACY-1215 可以显著抑制人原代软骨细胞和 C28/I2 细胞中炎症因子的表达，包括 IL-1β和 IL-6。此外，ACY-1215 通过抑制软骨细胞中基质降解蛋白酶（包括 MMP-1 和 MMP-13）的表达，发挥强大的软骨保护作用。这些作用可能与 ACY-1215 诱导的 OA 软骨细胞中 NF-κB 和 STAT3 通路的下调有关。综上所述，我们的研究结果表明，ACY-1215 可能是治疗 OA 的一种有潜力和有前途的治疗药物。
