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

Abstract

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.

The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?

“…Several of such alterations have been implicated in diseases or conditions relevant to menopause, such as osteoporosis and calcium signaling [83][84][85], cardiovascular disease [86,87], osteoarthritis [88][89][90], the nervous system and the brain [91][92][93][94], obesity [95,96], and vascular inflammation [97]. BB.…”

Exosomes loaded a smart bilayer-hydrogel scaffold with ROS-scavenging and macrophage-reprogramming properties for repairing cartilage defect

“…Exosomes (Exos) from bone marrow-derived mesenchymal stem cells (BMSCs) can recapitulate the effect of native cells on cartilage defects without the associated side effects of stem cells [ 7 , 8 ]. Abundant miR-23a-3p within Exos inhibits phosphatase and tensin homolog (PTEN) levels and enhances protein kinase B (AKT) expression, thus promoting cartilage regeneration [ 9 , 10 ].…”