Significance:

Osteoarthritis (OA), one of the most prevalent joint diseases affecting more than 240 million people, strongly influences human health and reduces life quality. This review aims to fill the current research gap regarding the application and potential of mitochondrial quality control (MQC) based therapies in the treatment of OA, thereby providing guidance for future research and clinical practice.

Recent Advances:

Chondrocytes respond to the inflammatory microenvironment via an array of signaling pathways and thus are critical in cartilage degeneration and OA progression. Mitochondria, as an important metabolic center in chondrocytes, play a vital role in responding to inflammatory stimuli. Multiple MQC mechanisms, including mitochondrial antioxidant defense, mitochondrial protein quality control, mitochondrial DNA repair, mitochondrial dynamics, mitophagy, and mitochondrial biogenesis, sustain mitochondrial homeostasis under pathological conditions.

Critical Issues:

Despite extensive OA research, effective therapies remain limited. Elucidating MQC mechanisms in disease progression and post-traumatic cartilage repair is crucial. While preclinical studies demonstrate potential, clinical translation requires addressing protocol standardization, patient stratification, and long-term efficacy, as well as safety validation.

Future Directions:

Future research should focus on developing personalized MQC-based OA therapies guided by biomarker profiling and signaling pathway modulation. However, translational challenges persist, particularly regarding pervasive off-target effects, inadequate OA-specific targeting capacity, interpatient heterogeneity, and reliable evaluation of long-term therapeutic efficacy. Strategic prioritization of OA-specific MQC targets coupled with delivery system optimization may significantly improve both clinical translatability and therapeutic outcomes.