Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis
Abstract Background 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,...
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-021-00940-2 |
| _version_ | 1811306110646222848 |
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| author | Shenglong Li Jie Liu Siyu Liu Weijie Jiao Xiaohong Wang |
| author_facet | Shenglong Li Jie Liu Siyu Liu Weijie Jiao Xiaohong Wang |
| author_sort | Shenglong Li |
| collection | DOAJ |
| description | Abstract Background 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. Results 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 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. Conclusion 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. Graphic abstract |
| first_indexed | 2024-04-13T08:39:39Z |
| format | Article |
| id | doaj.art-1d17d37f0aa344edab2e6d15fba44555 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-13T08:39:39Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-1d17d37f0aa344edab2e6d15fba445552022-12-22T02:53:57ZengBMCJournal of Nanobiotechnology1477-31552021-06-0119112010.1186/s12951-021-00940-2Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axisShenglong Li0Jie Liu1Siyu Liu2Weijie Jiao3Xiaohong Wang4Department of Tissue Engineering, Center of 3D Printing & Organ Manufacturing, School of Fundamental Sciences, China Medical University (CMU)Department of Prosthodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral DiseasesDepartment of Tissue Engineering, Center of 3D Printing & Organ Manufacturing, School of Fundamental Sciences, China Medical University (CMU)Department of Tissue Engineering, Center of 3D Printing & Organ Manufacturing, School of Fundamental Sciences, China Medical University (CMU)Department of Tissue Engineering, Center of 3D Printing & Organ Manufacturing, School of Fundamental Sciences, China Medical University (CMU)Abstract Background 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. Results 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 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. Conclusion 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. Graphic abstracthttps://doi.org/10.1186/s12951-021-00940-2Mesenchymal stem cells (MSCs)Extracellular vesiclesOsteoarthritisCircular RNA HIPK3 (circHIPK3)MiR-124-3pMYH9 |
| spellingShingle | Shenglong Li Jie Liu Siyu Liu Weijie Jiao Xiaohong Wang Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis Journal of Nanobiotechnology Mesenchymal stem cells (MSCs) Extracellular vesicles Osteoarthritis Circular RNA HIPK3 (circHIPK3) MiR-124-3p MYH9 |
| title | Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis |
| title_full | Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis |
| title_fullStr | Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis |
| title_full_unstemmed | Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis |
| title_short | Mesenchymal stem cell-derived extracellular vesicles prevent the development of osteoarthritis via the circHIPK3/miR-124-3p/MYH9 axis |
| title_sort | mesenchymal stem cell derived extracellular vesicles prevent the development of osteoarthritis via the circhipk3 mir 124 3p myh9 axis |
| topic | Mesenchymal stem cells (MSCs) Extracellular vesicles Osteoarthritis Circular RNA HIPK3 (circHIPK3) MiR-124-3p MYH9 |
| url | https://doi.org/10.1186/s12951-021-00940-2 |
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