The role of chondrocyte senescence in osteoarthritis pathogenesis and therapeutic implications
Kai Huang, Haili Cai
Abstract
Osteoarthritis (OA) is a common and debilitating joint disorder, with its pathogenesis significantly influenced by factors such as aging and obesity. A critical aspect of OA development is the senescence of chondrocytes, which is characterized by irreversible cell cycle arrest and the secretion of pro-inflammatory molecules, collectively known as the senescence-associated secretory phenotype (SASP). Senescent chondrocytes compromise the maintenance of the extracellular matrix (ECM) and accelerate cartilage degradation, thereby exacerbating the progression of OA. Contributing factors to chondrocyte senescence include oxidative stress, mechanical overload, and ECM stiffness, while cellular dysfunctions such as mitochondrial impairment and defective autophagy further promote cartilage deterioration. Emerging therapeutic strategies aim to target senescent chondrocytes through the use of senolytic and senomorphic agents, microRNA-based therapies, immunotherapies, and stem cell-based interventions. Although these treatments have demonstrated potential in preclinical studies, additional research is required to enhance their efficacy in the clinical management of OA. • Chondrocyte senescence drives cartilage degradation in osteoarthritis. • ECM stiffness and mechanical stress promote chondrocyte aging. • Mitochondrial dysfunction and autophagy defects accelerate OA progression. • Senolytics, miRNAs, and CAR-T offer new therapeutic options for OA. • Inflamm-aging impairs cartilage repair and worsens OA pathology.