Mitoquinone alleviates osteoarthritis progress by activating the NRF2-Parkin axis

Liangcai Hou; Genchun Wang; Xiong Zhang; Fan Lu; Jingting Xu; Zhou Guo; Jiamin Lin; Zehang Zheng; Haigang Liu; Yanjun Hou; Kai Sun; Fengjing Guo

doi:10.1016/j.isci.2023.107647

Mitoquinone alleviates osteoarthritis progress by activating the NRF2-Parkin axis

iScience. 2023 Aug 15;26(9):107647. doi: 10.1016/j.isci.2023.107647. eCollection 2023 Sep 15.

Authors

Liangcai Hou¹, Genchun Wang¹, Xiong Zhang¹, Fan Lu¹, Jingting Xu¹, Zhou Guo¹, Jiamin Lin², Zehang Zheng¹, Haigang Liu¹, Yanjun Hou¹, Kai Sun¹, Fengjing Guo¹

Affiliations

¹ Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
² Department of Plastic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou 318000, Zhejiang, P.R. China.

Abstract

Osteoarthritis (OA) is a prevalent degenerative disease of the elderly. The NRF2 antioxidant system plays a critical role in maintaining redox balance. Mitoquinone (MitoQ) is a mitochondria-targeted antioxidant. This research aimed to determine whether MitoQ alleviated OA and the role of the NRF2/Parkin axis in MitoQ-mediated protective effects. In interleukin (IL)-1β-induced OA chondrocytes, MitoQ activated the NRF2 pathway, reducing extracellular matrix (ECM) degradation and inflammation. MitoQ also increased glutathione peroxidase 4 (GPX4) expression, leading to decreased levels of reactive oxygen species (ROS) and lipid ROS. Silencing NRF2 weakened MitoQ's protective effects, while knockdown of Parkin upregulated the NRF2 pathway, inhibiting OA progression. Intra-articular injection of MitoQ mitigated cartilage destruction in destabilized medial meniscus (DMM)-induced OA mice. Our study demonstrates that MitoQ maintains cartilage homeostasis in vivo and in vitro through the NRF2/Parkin axis. We supplemented the negative feedback regulation mechanism between NRF2 and Parkin. These findings highlight the therapeutic potential of MitoQ for OA treatment.

Keywords: Cell biology; Molecular biology; Orthopedics.