Cell-free osteoarthritis treatment with dual-engineered chondrocyte-targeted extracellular vesicles derived from mechanical loading primed mesenchymal stem cells
Osteoarthritis (OA) is an age-related chronic inflammatory disease, predominantly characterized by chondrocyte senescence and extracellular matrix (ECM) degradation. Although mesenchymal stem cells (MSCs) derived extracellular vesicles (EVs) are promising for promoting cartilage regeneration, their...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2025-02-01
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| Series: | Journal of Tissue Engineering |
| Online Access: | https://doi.org/10.1177/20417314241312563 |
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| author | Peng Wang Haiyue Zhao Wei Chen Yuhui Guo Shuo Zhang Xin Xing Shuai Yang Fengkun Wang Juan Wang Zengwu Shao Yingze Zhang |
| author_facet | Peng Wang Haiyue Zhao Wei Chen Yuhui Guo Shuo Zhang Xin Xing Shuai Yang Fengkun Wang Juan Wang Zengwu Shao Yingze Zhang |
| author_sort | Peng Wang |
| collection | DOAJ |
| description | Osteoarthritis (OA) is an age-related chronic inflammatory disease, predominantly characterized by chondrocyte senescence and extracellular matrix (ECM) degradation. Although mesenchymal stem cells (MSCs) derived extracellular vesicles (EVs) are promising for promoting cartilage regeneration, their clinical application is limited by inconsistent therapeutic effects and insufficient targeting capabilities. Mechanical loading shows potential to optimize MSC-EVs for OA treatment, while the underlying mechanism is not clear. In this study, EVs derived from mechanical loading-primed MSCs (ML-EVs) demonstrate prominent efficacy in maintaining ECM homeostasis and relieving chondrocyte senescence, thereby mitigating OA. Subsequent miRNA sequencing reveals that ML-EVs exert their effects by delivering miR-27b-3p, which targets ROR1 mRNA in chondrocytes and suppresses downstream NF-κB pathways. By modulating the ROR1/NF-κB axis, miR-27b-3p effectively restrains ECM degradation and chondrocyte senescence. To optimize therapeutic efficacy of EVs, miR-27b-3p is overexpressed within EVs (miR OE -EVs), and a chondrocyte-targeted peptide (CTP) is conjugated to their surface, thereby constructing dual-engineered chondrocyte-targeted EVs (CTP/miR OE -EVs). CTP/miR OE -EVs exhibit excellent ability to specifically target cartilage and ameliorate OA pathology. In conclusion, this study underscores the critical role of mechanical loading in augmenting effectiveness of EVs in mitigating OA and introduces dual-engineered EVs that specifically target chondrocytes, providing a promising therapeutic strategy for OA. |
| format | Article |
| id | doaj-art-55de98206ec94624b8ec2b906e901b9f |
| institution | Kabale University |
| issn | 2041-7314 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of Tissue Engineering |
| spelling | doaj-art-55de98206ec94624b8ec2b906e901b9f2025-02-08T10:03:20ZengSAGE PublishingJournal of Tissue Engineering2041-73142025-02-011610.1177/20417314241312563Cell-free osteoarthritis treatment with dual-engineered chondrocyte-targeted extracellular vesicles derived from mechanical loading primed mesenchymal stem cellsPeng Wang0Haiyue Zhao1Wei Chen2Yuhui Guo3Shuo Zhang4Xin Xing5Shuai Yang6Fengkun Wang7Juan Wang8Zengwu Shao9Yingze Zhang10Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaDepartment of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaDepartment of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaDepartment of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, ChinaDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, ChinaOsteoarthritis (OA) is an age-related chronic inflammatory disease, predominantly characterized by chondrocyte senescence and extracellular matrix (ECM) degradation. Although mesenchymal stem cells (MSCs) derived extracellular vesicles (EVs) are promising for promoting cartilage regeneration, their clinical application is limited by inconsistent therapeutic effects and insufficient targeting capabilities. Mechanical loading shows potential to optimize MSC-EVs for OA treatment, while the underlying mechanism is not clear. In this study, EVs derived from mechanical loading-primed MSCs (ML-EVs) demonstrate prominent efficacy in maintaining ECM homeostasis and relieving chondrocyte senescence, thereby mitigating OA. Subsequent miRNA sequencing reveals that ML-EVs exert their effects by delivering miR-27b-3p, which targets ROR1 mRNA in chondrocytes and suppresses downstream NF-κB pathways. By modulating the ROR1/NF-κB axis, miR-27b-3p effectively restrains ECM degradation and chondrocyte senescence. To optimize therapeutic efficacy of EVs, miR-27b-3p is overexpressed within EVs (miR OE -EVs), and a chondrocyte-targeted peptide (CTP) is conjugated to their surface, thereby constructing dual-engineered chondrocyte-targeted EVs (CTP/miR OE -EVs). CTP/miR OE -EVs exhibit excellent ability to specifically target cartilage and ameliorate OA pathology. In conclusion, this study underscores the critical role of mechanical loading in augmenting effectiveness of EVs in mitigating OA and introduces dual-engineered EVs that specifically target chondrocytes, providing a promising therapeutic strategy for OA.https://doi.org/10.1177/20417314241312563 |
| spellingShingle | Peng Wang Haiyue Zhao Wei Chen Yuhui Guo Shuo Zhang Xin Xing Shuai Yang Fengkun Wang Juan Wang Zengwu Shao Yingze Zhang Cell-free osteoarthritis treatment with dual-engineered chondrocyte-targeted extracellular vesicles derived from mechanical loading primed mesenchymal stem cells Journal of Tissue Engineering |
| title | Cell-free osteoarthritis treatment with dual-engineered chondrocyte-targeted extracellular vesicles derived from mechanical loading primed mesenchymal stem cells |
| title_full | Cell-free osteoarthritis treatment with dual-engineered chondrocyte-targeted extracellular vesicles derived from mechanical loading primed mesenchymal stem cells |
| title_fullStr | Cell-free osteoarthritis treatment with dual-engineered chondrocyte-targeted extracellular vesicles derived from mechanical loading primed mesenchymal stem cells |
| title_full_unstemmed | Cell-free osteoarthritis treatment with dual-engineered chondrocyte-targeted extracellular vesicles derived from mechanical loading primed mesenchymal stem cells |
| title_short | Cell-free osteoarthritis treatment with dual-engineered chondrocyte-targeted extracellular vesicles derived from mechanical loading primed mesenchymal stem cells |
| title_sort | cell free osteoarthritis treatment with dual engineered chondrocyte targeted extracellular vesicles derived from mechanical loading primed mesenchymal stem cells |
| url | https://doi.org/10.1177/20417314241312563 |
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