Targeting regulated chondrocyte death in osteoarthritis therapy

In vivo articular cartilage degeneration is an essential hallmark of osteoarthritis (OA), involving chondrocyte senescence, extracellular matrix degradation, chondrocyte death, cartilage loss, and bone erosion. Among them, chondrocyte death is one of the major factors leading to cartilage degeneration. Many studies have reported that various cell death modes, including apoptosis, ferroptosis, and autophagy, play a key role in OA chondrocyte death. Currently, there is insufficient understanding of OA pathogenesis, and there remains a lack of treatment methods to prevent OA and inhibit its progression. Studies suggest that OA prevention and treatment are mainly directed to arrest premature or excessive chondrocyte death. In this review, we a) discuss the forms of death of chondrocytes and the associations between them, b) summarize the critical factors in chondrocyte death, c) discuss the vital role of chondrocyte death in OA, d) and, explore new approaches for targeting the regulation of chondrocyte death in OA treatment.