Unveiling the potential of MSC extracellular vesicles: MiR-122-5p enhancing chondrocyte regeneration in osteoarthritis via autophagy mechanism
Abstract Background Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases, while the mechanism by which extracellular vesicles (EVs) promote chondrocyte regeneration remains unclear. The study assessed the effect of hypoxic mesenchymal stem cells (MSCs)-derived EVs on cartilag...
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BMC
2025-06-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04412-4 |
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| author | Haifeng Zhang Yanmeng Yang Yingnan Wu Vinitha Denslin Yi Wei Justin Koh Ling Liu Wenhai Zhuo Wing Moon Raymond Lam Yinxian Yu James Hoi Po Hui Zheng Yang |
| author_facet | Haifeng Zhang Yanmeng Yang Yingnan Wu Vinitha Denslin Yi Wei Justin Koh Ling Liu Wenhai Zhuo Wing Moon Raymond Lam Yinxian Yu James Hoi Po Hui Zheng Yang |
| author_sort | Haifeng Zhang |
| collection | DOAJ |
| description | Abstract Background Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases, while the mechanism by which extracellular vesicles (EVs) promote chondrocyte regeneration remains unclear. The study assessed the effect of hypoxic mesenchymal stem cells (MSCs)-derived EVs on cartilage repair in a rat OA model. Methods The effects of EVs on chondrocyte regeneration and autophagy were evaluated in vitro. The influence of specific micro RNA (miRNA) and downstream target genes was examined following EV miRNA sequencing and multiple intersecting database analysis. Results We found EVs derived from hypoxia preconditioned human MSCs to promote cartilage repair in rat OA and enhance the proliferation and migration of chondrocytes in vitro, mediated via chondrocyte autophagy. MiRNA sequencing revealed a significant enrichment of miRNA122-5p in hypoxic MSCs EV, which through regulation of the target gene, DUSP2, mediated autophagy and participated in chondrocyte regeneration. DUSP2 regulation of chondrocyte autophagy could act via the phosphorylation of ERK1/2 and P38. Conclusions This study demonstrates that EVs released by MSCs under hypoxic conditions have a beneficial effect on chondrocyte regeneration. A novel mechanism for chondrocyte autophagy is mediated by miR122-5P and DUSP2 target molecules, providing new insights into OA treatments. |
| format | Article |
| id | doaj-art-1cfc90a92cf644a1bb07e13037b2c6eb |
| institution | DOAJ |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-1cfc90a92cf644a1bb07e13037b2c6eb2025-08-20T03:10:38ZengBMCStem Cell Research & Therapy1757-65122025-06-0116111710.1186/s13287-025-04412-4Unveiling the potential of MSC extracellular vesicles: MiR-122-5p enhancing chondrocyte regeneration in osteoarthritis via autophagy mechanismHaifeng Zhang0Yanmeng Yang1Yingnan Wu2Vinitha Denslin3Yi Wei Justin Koh4Ling Liu5Wenhai Zhuo6Wing Moon Raymond Lam7Yinxian Yu8James Hoi Po Hui9Zheng Yang10Department of Orthopedic Surgery, Yong Loo Lin School of Medicine, National University of SingaporeCritical Analytics for Manufacturing Personalised-Medicine, Singapore-MIT Alliance for Research and TechnologyDepartment of Orthopedic Surgery, Yong Loo Lin School of Medicine, National University of SingaporeNUS Tissue Engineering Program, Life Sciences Institute, National University of SingaporeDepartment of Orthopedic Surgery, Yong Loo Lin School of Medicine, National University of SingaporeResearch Office, Sengkang General HospitalDepartment of Orthopedic Surgery, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Orthopedic Surgery, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Orthopaedic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Orthopedic Surgery, Yong Loo Lin School of Medicine, National University of SingaporeDepartment of Orthopedic Surgery, Yong Loo Lin School of Medicine, National University of SingaporeAbstract Background Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases, while the mechanism by which extracellular vesicles (EVs) promote chondrocyte regeneration remains unclear. The study assessed the effect of hypoxic mesenchymal stem cells (MSCs)-derived EVs on cartilage repair in a rat OA model. Methods The effects of EVs on chondrocyte regeneration and autophagy were evaluated in vitro. The influence of specific micro RNA (miRNA) and downstream target genes was examined following EV miRNA sequencing and multiple intersecting database analysis. Results We found EVs derived from hypoxia preconditioned human MSCs to promote cartilage repair in rat OA and enhance the proliferation and migration of chondrocytes in vitro, mediated via chondrocyte autophagy. MiRNA sequencing revealed a significant enrichment of miRNA122-5p in hypoxic MSCs EV, which through regulation of the target gene, DUSP2, mediated autophagy and participated in chondrocyte regeneration. DUSP2 regulation of chondrocyte autophagy could act via the phosphorylation of ERK1/2 and P38. Conclusions This study demonstrates that EVs released by MSCs under hypoxic conditions have a beneficial effect on chondrocyte regeneration. A novel mechanism for chondrocyte autophagy is mediated by miR122-5P and DUSP2 target molecules, providing new insights into OA treatments.https://doi.org/10.1186/s13287-025-04412-4OsteoarthritisChondrocyteExtracellular vesiclesAutophagymiR-122-5pDUSP2 |
| spellingShingle | Haifeng Zhang Yanmeng Yang Yingnan Wu Vinitha Denslin Yi Wei Justin Koh Ling Liu Wenhai Zhuo Wing Moon Raymond Lam Yinxian Yu James Hoi Po Hui Zheng Yang Unveiling the potential of MSC extracellular vesicles: MiR-122-5p enhancing chondrocyte regeneration in osteoarthritis via autophagy mechanism Stem Cell Research & Therapy Osteoarthritis Chondrocyte Extracellular vesicles Autophagy miR-122-5p DUSP2 |
| title | Unveiling the potential of MSC extracellular vesicles: MiR-122-5p enhancing chondrocyte regeneration in osteoarthritis via autophagy mechanism |
| title_full | Unveiling the potential of MSC extracellular vesicles: MiR-122-5p enhancing chondrocyte regeneration in osteoarthritis via autophagy mechanism |
| title_fullStr | Unveiling the potential of MSC extracellular vesicles: MiR-122-5p enhancing chondrocyte regeneration in osteoarthritis via autophagy mechanism |
| title_full_unstemmed | Unveiling the potential of MSC extracellular vesicles: MiR-122-5p enhancing chondrocyte regeneration in osteoarthritis via autophagy mechanism |
| title_short | Unveiling the potential of MSC extracellular vesicles: MiR-122-5p enhancing chondrocyte regeneration in osteoarthritis via autophagy mechanism |
| title_sort | unveiling the potential of msc extracellular vesicles mir 122 5p enhancing chondrocyte regeneration in osteoarthritis via autophagy mechanism |
| topic | Osteoarthritis Chondrocyte Extracellular vesicles Autophagy miR-122-5p DUSP2 |
| url | https://doi.org/10.1186/s13287-025-04412-4 |
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