Yanqiu Sun, Jian Liu, Mingyu He, Dan Huang, Yuan Wang

Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, 230038, People’s Republic of China

Correspondence: Jian Liu, Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, 117 Meishan Road, Hefei, Anhui, 230038, People’s Republic of China, Tel +8613955109537, Email liujianahzy@126.com

Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that can lead to joint deformities, functional loss, and a significant reduction in patients’ quality of life. It also imposes a considerable medical and socio-economic burden. Iron-induced cell death, or ferroptosis, is a unique form of programmed cell death characterized by dysregulated iron metabolism and the accumulation of lipid peroxides resulting from increased reactive oxygen species (ROS) and reduced activity of glutathione peroxidase 4 (GPX4). The accumulation of lipid peroxides can cause cellular damage, promotes inflammatory responses and joint destruction. This process not only plays a crucial role in the pathogenesis of RA, but also provides new therapeutic targets for its treatment. In this review, we summarize the regulatory mechanisms of ferroptosis in the pathogenesis of RA. These include its roles in regulating oxidative stress and lipid peroxidation, inhibiting the abnormal proliferation of synovial fibroblasts (FLSs), preventing cartilage erosion, restoring immune homeostasis and inflammatory responses, and other aspects. Finally, we also discuss the potential clinical applications, and future prospects of ferroptosis-based therapies for RA treatment.

Keywords: ferroptosis, rheumatoid arthritis, treatment strategy, review