Ubiquitination and Deubiquitination in Osteoarthritis: From Mechanisms to Therapeutic Advances

Chronic osteoarthritis (OA) is distinguished by the deterioration of cartilage within joints, resulting in pain and reduced joint function.With the aging of the population, the prevalence of OA is increasing, becoming a public health issue. Despite ongoing research, the exact pathogenesis of OA remains unclear, limiting the development of effective treatment strategies.The system involving ubiquitin and proteasomes is of vital importance in the pathogenesis of osteoarthritis, with deubiquitinating enzymes (DUBs) regulating protein stability, activity, and localization, which are essential for maintaining cellular homeostasis. Aberrant DUB expression or dysfunction is closely associated with OA. DUBs exert a key role in modulating cellular signaling, inflammatory responses, and extracellular matrix degradation, which are processes related to OA, making them a new target for therapeutic research. However, DUB research is still in its infancy, and more basic research and clinical trials are needed to verify their safety and efficacy. This analysis condenses the operational mechanisms of Deubiquitinating Enzymes (DUBs) in osteoarthritis (OA) and explores prospective treatment approaches, discussing the challenges and future prospects of modulating the expression of E3 ubiquitin ligases and deubiquitinating enzymes to improve the therapeutic effects for patients with osteoarthritis, aiming to promote the development of more effective OA treatment strategies.