Exploration and breakthrough in the mode of chondrocyte death - A potential new mechanism for osteoarthritis

Osteoarthritis (OA) is a frequent chronic joint disease in orthopedics that effects individuals and society significantly. Obesity, aging, genetic susceptibility, and joint misalignment are all known risk factors for OA, but its pathomechanism is still poorly understood. Researches have revealed that OA is a much complex process related to inflammation, metabolic and chondrocyte death. It can affect all parts of the joint and is characterized by causing chondrocyte death and extracellular matrix descent. Previously, OA was thought to develop from excessive mechanical loading leading to the destruction of articular cartilage. Since some programmed cell deaths and OA share a pattern of chondrocyte destruction, it is likely that OA also involves programmed cell death. Even though chondrocyte apoptosis and pyroptosis have been investigated in OA, clarifing solely conventional cell death pathways is still insufficient to understand the pathophysiology of osteoarthritis. With more researches, it has been discovered that osteoarthritis and other new cell death processes, including PANoptosis, ferroptosis, and cell senescence, are strongly associated. Among these, PANoptosis combines the key traits of pyroptosis, cell apoptosis, and necrotic apoptosis into a highly coordinated and dynamically balanced programmed inflammatory cell death mechanism. Furthermore, we think that PANopotosis might obstruct necroptosis and cell senescence. Therefore, in order to offer direction for therapeutic treatment, we evaluate the development of research on multiple cell death of chondrocytes in OA.