Crosstalk between programmed cell death in chondrocytes-a molecular mechanism of osteoarthritis

Abstract

The pathogenesis of osteoarthritis (OA), particularly knee osteoarthritis, is unknown, which is a chronic inflammatory systemic disease. Pathologically, the disease is primarily defined by alterations including cartilage degeneration and joint space decrease, which can result in joint deformity and loss of function. While the drugs currently used to treat OA can be helpful, their adverse effects are so obvious that they need to be further modified. Therefore, a detailed analysis of the mechanisms underlying the initiation and progression of OA is necessary to identify novel treatment targets. Much emphasis has been paid to the significant role that programmed cell death (PCD) plays in OA, particularly in chondrocytes and synoviocytes, where PCD is particularly dysregulated. This paper summarizes the regulatory roles of several types of PCD in OA, including the apoptosis, necroptosis, and autophagy as well as the more recently identified NETosis, pyroptosis, ferroptosis, and cuproptosis. We also discuss the regulatory roles of these processes in chondrocytes, synoviocytes, and other cells. These findings not only provide a vital theoretical basis for enhancing clinical OA treatment practices, but they also point the way toward the development of new target drugs.