Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy
Zhong‐Hai Shen, Kang Ji, Zhenhai Cai, Chenglong Huang, Xiaojun He, Hongwei Xu, Gang Chen
Abstract
. TubA treatment effectively inhibits the expression of HDAC6, attenuates oxidative stress, reduces the level of apoptotic proteins to maintain chondrocyte survival, and suppresses the extracellular matrix (ECM) degradation. In addition, our results also revealed that HDAC6 inhibition by TubA activates autophagy in chondrocytes, whereas the protective effects of TubA were abolished by autophagy inhibitor intervention. Subsequently, the positive effects of HDAC6 inhibition by TubA were also found in a mouse OA model. Therefore, our study provide evidence that HDAC6 inhibition prevents OA development, and HDAC6 could be applied as a potential therapeutic target for OA management.