The Role of Ferroptosis in the Pathogenesis of Osteoarthritis

Osteoarthritis (OA) is the most common type of arthritis. Its high prevalence, especially in the elderly, and its negative impact on physical function make it a leading cause of disability in the elderly. Joint pain as well joint stiffness are the common classic signs of OA. Chondrocyte death together with loss of articular cartilage integrity are the main pathologic changes in OA. Non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are commonly used for the management of OA; still, their effectiveness is limited, and no therapeutic strategy is able to fully stop OA progression. Ferroptosis is a kind of cell death, distinct from apoptosis and necroptosis, caused by iron-dependent peroxidation of membrane phospholipids that terminates cell life by disintegrating all plasma membranes. It has been suggested that ferroptosis has a critical role in decreased viability of chondrocytes in OA, and here, we review recent findings regarding the pathologic pathways that lead to chondrocyte ferroptosis, and discuss the possible therapeutic utility of ferroptosis inhibition in OA.