Progress in research on the association between mesenchymal stem cell senescence and knee osteoarthritis.

Osteoarthritis (OA) is an age-related disease characterized by cartilage degeneration, subchondral bone remodeling, and chronic low-grade inflammation, with knee osteoarthritis (KOA) being a leading cause of functional impairment and reduced quality of life in middle-aged and elderly individuals. In recent years, advances in stem cell biology and aging research have highlighted the critical role of mesenchymal stem cells (MSCs) in maintaining joint homeostasis, regulating inflammatory responses, and mediating cartilage repair. Accumulating evidence indicates that reductions in MSC quantity and functional decline-particularly age-associated decreases in proliferative capacity, impaired differentiation potential, mitochondrial dysfunction, and activation of the senescence-associated secretory phenotype (SASP)-constitute key biological mechanisms driving KOA onset and progression.This review systematically summarizes the major molecular mechanisms underlying MSC senescence, including telomere shortening, DNA damage accumulation, mitochondrial dysregulation, and SASP activation, and emphasizes the roles of senescent MSCs in impaired cartilage regenerative capacity, disruption of extracellular matrix homeostasis, and imbalance in inflammatory and immune microenvironments. Additionally, we highlight recent research on potential interventions targeting MSC senescence, including senescent cell clearance, metabolic and mitochondrial restoration, MSC-derived exosome therapy, and advances in engineered culture and delivery technologies.In conclusion, MSC senescence represents not only a fundamental pathological basis for KOA development but also a critical target for future OA interventions, providing important theoretical and translational value for advancing regenerative medicine strategies toward clinical application.