Single-cell sequencing, genetics, and epigenetics reveal mesenchymal stem cell senescence in osteoarthritis (Review)

Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration, secondary bone hyperplasia, inadequate extracellular matrix synthesis and degeneration of articular cartilage. Mesenchymal stem cells (MSCs) can self-renew and undergo multidirectional differentiation; they can differentiate into chondrocytes. Aging MSCs have a weakened ability to differentiate, and release various pro-inflammatory cytokines, which may contribute to OA progression; the other mechanism contributing to OA is epigenetic regulation (for instance, DNA methylation, histone modification and regulation of non-coding RNA). Owing to the self-renewal and differentiation ability of MSCs, various MSC-based exogenous cell therapies have been developed to treat OA. The efficacy of MSC-based therapy is mainly attributed to cytokines, growth factors and the paracrine effect of exosomes. Recently, extensive studies have been conducted on MSC-derived exosomes. Exosomes from MSCs can deliver a variety of DNA, RNA, proteins and lipids, thereby facilitating MSC migration and cartilage repair. Therefore, MSC-derived exosomes are considered a promising therapy for OA. The present review summarized the association between MSC aging and OA in terms of genetics and epigenetics, and characteristics of MSC-derived exosomes, and the mechanism to alleviate OA cartilage damage.