Abstract
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
Highlights
Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) may play a vital role in a variety of biological processes, including cartilage regeneration
We found that circHIPK3, which is derived from MSCs-EVs, remarkedly promote chondrocyte proliferation, migration and suppress apoptosis
The results indicated that, compared with the control group, MSCs-circHIPK3-EVs treatment could lead to obviously higher expression of Collagen type II alpha chain (COL2A1), Aggrecan, and SRY-box transcription factor 9 (SOX9), and notably lower expression of MMP13 and RUNX family transcription factor 2 (Runx2) in chondrocytes (Fig. 3A, B)
Summary
Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) may play a vital role in a variety of biological processes, including cartilage regeneration. Few studies reported their potential in the development of osteoarthritis (OA) previously. We explored the biological roles and underlying mechanism of MSCs-EVs in OA. Osteoarthritis (OA) is a common degenerative disorder of the joints that accounts for major physical pain in older adults [1, 2]. Studies indicate that the incidence of OA increases annually worldwide [7], which has a strong impact on the labor ability and quality of life of patients, and brings a huge economic burden. The occurrence and development of OA are associated with complex interactions among many factors, such as mechanical, cellular, and biochemical factors [8], while the pathogenesis of OA remains unclear. Exploring the novel therapeutic approach for OA is critical
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