Yikai Liu,1,2 Zian Zhang,2 Yuan Fang,2 Chang Liu,2 Haining Zhang2 

1Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, People’s Republic of China; 2Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China

Correspondence: Haining Zhang, Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China, Tel +86-18661800365, Email zhanghaining1976@126.com

Abstract: Osteoarthritis (OA) is a prevalent degenerative disease in elderly people that is characterized by cartilage loss and abrasion, leading to joint pain and dysfunction. The aetiology of OA is complicated and includes abnormal mechanical stress, a mild inflammatory environment, chondrocyte senescence and apoptosis, and changes in chondrocyte metabolism. Ferroptosis is a regulated cell death modality characterized by the excessive accumulation of lipid peroxidation and mitochondrial dysfunction. The role of ferroptosis in OA pathogenesis has aroused researchers’ attention in the past two years, and there is mounting evidence indicating that ferroptosis is destructive. However, the impact of ferroptosis on OA and how the regulators of ferroptosis affect OA development are unclear. Here, we reviewed the current understanding of ferroptosis in OA pathogenesis and summarized several drugs and compounds targeting ferroptosis in OA treatment. The accumulation of intracellular iron, the trigger of Fenton reaction, the excessive production of ROS, the peroxidation of PUFA-PLs, and mitochondrial and membrane damage are involved in chondrocyte ferroptosis. System Xc− and GPX4 are the most important regulators that control ferroptosis. Several compounds, such as DFO and Fer-1, have been proven effective in preventing ferroptosis and slowing OA progression on animal models. Collectively, targeting ferroptosis shows great potential in treating OA.

Keywords: ferroptosis, osteoarthritis, chondrocyte, lipid peroxidation, iron metabolism