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

Journal of Nanobiotechnology

Jie Liu¹  Weijie Jiao²  Siyu Liu²  Xiaohong Wang³  Shenglong Li⁴ 

[1] Department of Prosthodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, 110002, Shenyang, China;Department of Tissue Engineering, Center of 3D Printing & Organ Manufacturing, School of Fundamental Sciences, China Medical University (CMU), No. 77 Puhe Road, Shenyang North New Area, 110122, Shenyang, China;Department of Tissue Engineering, Center of 3D Printing & Organ Manufacturing, School of Fundamental Sciences, China Medical University (CMU), No. 77 Puhe Road, Shenyang North New Area, 110122, Shenyang, China;Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, 100084, Beijing, China;Department of Tissue Engineering, Center of 3D Printing & Organ Manufacturing, School of Fundamental Sciences, China Medical University (CMU), No. 77 Puhe Road, Shenyang North New Area, 110122, Shenyang, China;Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, 110042, Shenyang, Liaoning Province, China;

关键词: Mesenchymal stem cells (MSCs);    Extracellular vesicles;    Osteoarthritis;    Circular RNA HIPK3 (circHIPK3);    MiR-124-3p;    MYH9;   

DOI  :  10.1186/s12951-021-00940-2

来源: Springer

【 摘 要 】

BackgroundExtracellular 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.ResultsCo-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 interleukin1β (IL-1β) induction. In addition, MSCs-circHIPK3-EVs (EVs derived from MSCs overexpressing circHIPK3) considerably improved IL-1β-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.ConclusionThe 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.Graphic abstract

【 授权许可】

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