{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T10:33:49Z","timestamp":1793010829345,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92368201"],"award-info":[{"award-number":["92368201"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272530"],"award-info":[{"award-number":["82272530"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372459"],"award-info":[{"award-number":["82372459"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82502961"],"award-info":[{"award-number":["82502961"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024T170409"],"award-info":[{"award-number":["2024T170409"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["14380493"],"award-info":[{"award-number":["14380493"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["14380494"],"award-info":[{"award-number":["14380494"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Skeletal muscle injuries significantly impair mobility and function, yet effective therapeutic interventions remain limited. Both eccentric exercise (EE) and concentric exercise (CE) promote muscle repair, but the underlying mechanisms are not fully understood. Muscle\u2010derived extracellular vesicles (mEVs) have emerged as critical mediators of intercellular communication; however, their role in exercise\u2010induced regeneration remains unclear.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A murine model of barium chloride\u2010induced muscle injury was used to compare the effects of EE and CE on muscle regeneration. mEVs were isolated from sedentary (SED), CE\u2010 and EE\u2010conditioned muscle and characterised by nanoparticle tracking analysis, transmission electron microscopy and western blotting. Metabolic profiling of mEVs was performed using LC\u2013MS. The functional roles were assessed through intramuscular injection of mEVs and GW4869\u2010mediated inhibition of mEV secretion. The effects of mEVs on myogenesis were further examined in C2C12 myoblasts.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n EE significantly enhanced muscle regeneration compared with CE, as evidenced by improved histology, reduced fibrosis (\n F<\/jats:italic>\n (2,15)\u2009=\u200959.37,\n p<\/jats:italic>\n \u2009<\u20090.0001) and increased expression of myogenic markers such as Myod (\n p<\/jats:italic>\n \u2009<\u20090.001), Myog (\n p<\/jats:italic>\n \u2009<\u20090.001) and eMyhc (\n p<\/jats:italic>\n \u2009<\u20090.001). EE also induced greater release of mEVs than CE, as indicated by higher expression of mEV markers and Rab27a\/b (Rab27a,\n p<\/jats:italic>\n \u2009<\u20090.001; Rab27b,\n p<\/jats:italic>\n \u2009=\u20090.1222). Inhibition of mEV secretion with GW4869 abolished the regenerative benefits of exercise. Exogenous administration of EE\u2010mEVs enhanced muscle repair and C2C12 differentiation (Myod,\n F<\/jats:italic>\n (2, 6)\u2009=\u200933.09,\n p<\/jats:italic>\n \u2009<\u20090.001; Myog,\n F<\/jats:italic>\n (2, 6)\u2009=\u200966.41,\n p<\/jats:italic>\n \u2009<\u20090.001) more effectively than CE\u2010mEVs or SED\u2010mEVs. Metabolomic analysis revealed significant enrichment of lipid metabolites in EE\u2010mEVs (\n N<\/jats:italic>\n \u2009=\u20095,\n p<\/jats:italic>\n \u2009<\u20090.05), which was consistent with the upregulation of lipid metabolism\u2013related genes. RNA\u2010seq analyses further indicated that lipid metabolites enriched in mEVs contributed to muscle repair potentially through activation of energy\u2010sensing pathways such as AMPK.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n EE facilitates muscle repair more effectively than CE by promoting the release of mEVs enriched in pro\u2010regenerative lipid metabolites. These findings suggest EE\u2010mEVs as a promising biological therapeutic strategy for muscle injury, particularly in cases where exercise is not feasible.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70374","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:05:16Z","timestamp":1787983516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Skeletal Muscle\u2013Derived Extracellular Vesicles During Eccentric and Concentric Exercise Promote Muscle Regeneration After Injury"],"prefix":"10.1002","volume":"17","author":[{"given":"Yining","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing Jiangsu China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaquan","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing Jiangsu China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University Nanjing Jiangsu China"},{"name":"Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing Jiangsu China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University Nanjing Jiangsu China"},{"name":"Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"An","sequence":"additional","affiliation":[{"name":"Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing Jiangsu China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University Nanjing Jiangsu China"},{"name":"Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing Jiangsu China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University Nanjing Jiangsu China"},{"name":"Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haosheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing Jiangsu China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University Nanjing Jiangsu China"},{"name":"Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation Nanjing Jiangsu 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University Nanjing Jiangsu China"},{"name":"Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing Jiangsu China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University Nanjing Jiangsu China"},{"name":"Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Shen","sequence":"additional","affiliation":[{"name":"Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing Jiangsu China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University Nanjing Jiangsu China"},{"name":"Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University Nanjing Jiangsu China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University Nanjing Jiangsu China"},{"name":"Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation Nanjing Jiangsu 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2015-095559"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25151"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.12965\/jer.1836440.220"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsm.2008.051417"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00447"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12601"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0190-0"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2023.12.011"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-59959-w"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029827"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.76"},{"key":"e_1_2_9_13_1","first-page":"4609","article-title":"Myogenic Exosome miR\u2010140\u20105p Modulates Skeletal Muscle Regeneration and Injury Repair by Regulating Muscle Satellite Cells","volume":"16","author":"Cao X.","year":"2024","journal-title":"Aging (Albany 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