Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis

• Published in: Journal of nanobiotechnology Vol. 19; no. 1; pp. 1 - 20
• Main Authors: Li, Shenglong, Liu, Jie, Liu, Siyu, Jiao, Weijie, Wang, Xiaohong
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 30.06.2021; BioMed Central; BMC
• Subjects: Aggrecan; Apoptosis; Arthritis; Biological activity; Biological products; Biomedical materials; Bone marrow; Care and treatment; Cartilage; Cartilage diseases; Cbfa-1 protein; Cell culture; Cell growth; Cell organelles; Cellular signal transduction; Chondrocytes; Circular RNA HIPK3 (circHIPK3); Collagen (type II); Collagenase 3; Development and progression; Extracellular vesicles; Gene expression; Genetic aspects; Genomes; Growth factors; Health aspects; Hypertrophy; IL-1β; Kinases; Matrix metalloproteinases; Medical research; Mesenchymal stem cells; Mesenchymal stem cells (MSCs); Metalloproteinase; MiR-124-3p; MYH9; Osteoarthritis; Pathogenesis; Physiological aspects; Proteins; Regeneration; Sox9 protein; Stem cell transplantation; Stem cells; Therapeutics, Experimental; Vesicles; China
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-021-00940-2

Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) may play a vital role in a variety of biological processes, including cartilage regeneration. However, few studies reported their potential in the development of osteoarthritis (OA) previously. In this study, we explored the biological roles and underlying mechanism of MSCs-EVs in OA. Co-culture experiments revealed that MSCs-EVs could promote the expression of collagen type II alpha 1 chain (COL2A1), SRY-box transcription factor 9 (SOX9) and Aggrecan while negatively regulate the expression of chondrocyte hypertrophy markers matrix metallopeptidase 13 (MMP-13) and RUNX family transcription factor 2 (Runx2) in mouse chondrocytes in the OA model. Besides, the results of cell experiments indicated that MSCs-EVs could notably weaken the suppression of chondrocyte proliferation, migration and the promotion of chondrocyte apoptosis via interleukin1[beta] (IL-1[beta]) induction. In addition, MSCs-circHIPK3-EVs (EVs derived from MSCs overexpressing circHIPK3) considerably improved IL-1[beta]-induced chondrocyte injury. Mechanistically, we elucidated that circHIPK3 could directly bind to miR-124-3p and subsequently elevate the expression of the target gene MYH9. The findings in our study demonstrated that EVs-circHIPK3 participated in MSCs-EVs-mediated chondrocyte proliferation and migration induction and in chondrocyte apoptosis inhibition via the miR-124-3p/MYH9 axis. This offers a promising novel cell-free therapy for treating OA.