Objective: Osteoarthritis (OA) is a common disease with complex and unclear pathogenesis. Ferroptosis is a new cell death mode, which is proved to be involved in different kinds of disease. We hypothesized that ferroptosis contributes to the progress of human OA.
Design: Chondrocytes were extracted from waste cartilage of total knee arthroplasty, and stimulated with interleukin-1β (IL-1β). Then, we detected the morphology, proliferation, and viability, and levels of Fe3+, glutathione (GSH), reactive oxygen species (ROS), malondialdehyde (MDA), and 5 proteins related to ferroptosis with or without intervention of ferrostatin-1 (Fer-1). In addition, we compared the effect of Fer-1 and liproxstatin-1 (Lip-1) on ferroptosis and the protection of chondrocytes by detecting several markers of both ferroptosis and OA.
Results: After stimulation of IL-1β, there were significant changes on the shape of chondrocyte, with lower viability and proliferation. There was accumulation of intracellular Fe3+, GSH, ROS, and MDA, with the changes of expression of 5 ferroptosis-related proteins. With the contribution of Fer-1, results above were reversed. Moreover, there was no significant difference in GPX4 and ACSL4 between Fer-1 and Lip-1 group. However, the expression of COLX, ADAMTS5, and MMP-13 are lower after the treatment of Fer-1 compared with Lip-1.
Conclusions: Ferroptosis plays an important role in human OA chondrocytes, which can be reversed by Fer-1, illustrating that inhibitor of ferroptosis may be a potential treatment of OA. Moreover, Lip-1 and Fer-1 can both alleviate the level of ferroptosis in OA chondrocytes, but Fer-1 had a more protective effect.
Keywords: chondrocyte; ferroptosis; ferrostatin-1; osteoarthritis.