Reactivating mitochondrial quality control via the Nrf2 pathway to combat metabolic stress in diabetic osteoarthritis.

The intersection of diabetes mellitus (DM) and osteoarthritis (OA) defines a distinct metabolic phenotype, commonly termed diabetic osteoarthritis (DOA), in which systemic metabolic toxicity independently accelerates articular degeneration. In addition to shared risk factors, this review delineates the molecular framework of DOA, detailing how persistent hyperglycemia initiates oxidative stress, chronic inflammation, and the accumulation of advanced glycation end products (AGEs), disrupting chondrocyte bioenergetic homeostasis. A pivotal event in this process is the dysregulation of mitochondrial quality control (MQC), a central regulatory mechanism that maintains cellular viability under metabolic stress. We further emphasize the dysregulation of the Nrf2 signaling pathway as a critical upstream determinant of mitochondrial dysfunction. By integrating epidemiological findings with mechanistic evidence, we propose that therapeutic restoration of the Nrf2-MQC axis may offer a rational strategy to preserve mitochondrial integrity and slow the progression of diabetes-associated joint degeneration.