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

Int J Mol Med. 2024 Jan;53(1):2. doi: 10.3892/ijmm.2023.5326. Epub 2023 Nov 8.

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.

Keywords: epigenetics; exosomes; genetics; mesenchymal stem cells; osteoarthritis; single‑cell sequencing.

Publication types

  • Review

MeSH terms

  • Cartilage, Articular* / metabolism
  • Cell Differentiation / genetics
  • Chondrocytes / metabolism
  • Cytokines / metabolism
  • Epigenesis, Genetic
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Humans
  • Mesenchymal Stem Cells* / metabolism
  • Osteoarthritis* / genetics
  • Osteoarthritis* / metabolism
  • Osteoarthritis* / therapy

Substances

  • Cytokines

Grants and funding

The present study was supported by the National Natural Science Foundation of China (grant nos. 81800785, 81972085 and 82172465), the China University Industry-University-Research Innovation Fund (grant no. 2021JH037), the Natural Science Foundation of Guangdong (grant nos. 2018A0303100027 and 2021A1515010706), the Guangdong Provincial Key Clinical Discipline-Orthopedics (grant no. 2000005), the Sanming Project of Shenzhen Health and Family Planning Commission (grant no. SZSM201612086), the Shenzhen Science and Technology Planning (grant nos. JCYJ20180228163401333 and JCYJ20190806170612680), the Shenzhen Key Medical Discipline Construction Fund (grant no. SZXK025), the discipline construction Capacity Improvement project of Shenzhen Municipal Health Commission (grant no. SZXJ2018065) and the Natural Science Foundation of Guangdong (grant no. 2023A1515010102).