{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:45:09Z","timestamp":1790898309135,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M661806"],"award-info":[{"award-number":["2019M661806"]}],"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":["14380494"],"award-info":[{"award-number":["14380494"]}],"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":["14380493"],"award-info":[{"award-number":["14380493"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010023","name":"Natural Science Research of Jiangsu Higher Education Institutions of China","doi-asserted-by":"publisher","award":["BK20200117"],"award-info":[{"award-number":["BK20200117"]}],"id":[{"id":"10.13039\/501100010023","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010023","name":"Natural Science Research of Jiangsu Higher Education Institutions of China","doi-asserted-by":"publisher","award":["BK20200314"],"award-info":[{"award-number":["BK20200314"]}],"id":[{"id":"10.13039\/501100010023","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972124"],"award-info":[{"award-number":["81972124"]}],"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":["82000069"],"award-info":[{"award-number":["82000069"]}],"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":["82002370"],"award-info":[{"award-number":["82002370"]}],"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":["81991514"],"award-info":[{"award-number":["81991514"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018635","name":"Thousand Young Talents Program of China","doi-asserted-by":"publisher","award":["13004001"],"award-info":[{"award-number":["13004001"]}],"id":[{"id":"10.13039\/501100018635","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFC2004900"],"award-info":[{"award-number":["2020YFC2004900"]}],"id":[{"id":"10.13039\/501100012166","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":[[2022,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Sarcopenia is a common and progressive skeletal muscle disorder characterized by atrophic muscle fibres and contractile dysfunction. Accumulating evidence shows that the number and function of satellite cells (SCs) decline and become impaired during ageing, which may contribute to impaired regenerative capacity. A series of myokines\/small extracellular vesicles (sEVs) released from muscle fibres regulate metabolism in muscle and extramuscular tissues in an autocrine\/paracrine\/endocrine manner during muscle atrophy. It is still unclear whether myokines\/sEVs derived from muscle fibres can affect satellite cell function during ageing.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Aged mice were used to investigate changes in the myogenic capacity of SCs during ageing\u2010induced muscle atrophy. The effects of atrophic myotube\u2010derived sEVs on satellite cell differentiation were investigated by biochemical methods and immunofluorescence staining. Small RNA sequencing was performed to identify differentially expressed sEV microRNAs (miRNAs) between the control myotubes and atrophic myotubes. The target genes of the miRNA were predicted by bioinformatics analysis and verified by luciferase activity assays. The effects of identified miRNA on the myogenic capacity of SCs in vivo were investigated by intramuscular injection of adeno\u2010associated virus (AAV) to overexpress or silence miRNA in skeletal muscle.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Our study showed that the myogenic capacity of SCs was significantly decreased (50%,\n n<\/jats:italic>\n \u00a0=\u00a06,\n P<\/jats:italic>\n \u00a0<\u00a00.001) in the tibialis anterior muscle of aged mice. We showed that atrophic myotube\u2010derived sEVs inhibited satellite cell differentiation in vitro (\n n<\/jats:italic>\n \u00a0=\u00a03,\n P<\/jats:italic>\n \u00a0<\u00a00.001) and in vivo (35%,\n n<\/jats:italic>\n \u00a0=\u00a06,\n P<\/jats:italic>\n \u00a0<\u00a00.05). We also found that\n miR\u2010690<\/jats:italic>\n was the most highly enriched miRNA among all the screened sEV miRNAs in atrophic myotubes [Log\n 2<\/jats:sub>\n (Fold Change)\u00a0=\u00a07,\n P<\/jats:italic>\n \u00a0<\u00a00.001], which was verified in the atrophic muscle of aged mice (threefold,\n n<\/jats:italic>\n \u00a0=\u00a06,\n P<\/jats:italic>\n \u00a0<\u00a00.001) and aged men with mean age of 71\u00a0\u00b1\u00a05.27\u00a0years (2.8\u2010fold,\n n<\/jats:italic>\n \u00a0=\u00a010,\n P<\/jats:italic>\n \u00a0<\u00a00.001).\n MiR\u2010690<\/jats:italic>\n can inhibit myogenic capacity of SCs by targeting myocyte enhancer factor 2, including\n Mef2a<\/jats:italic>\n ,\n Mef2c<\/jats:italic>\n and\n Mef2d<\/jats:italic>\n , in vitro (\n n<\/jats:italic>\n \u00a0=\u00a03,\n P<\/jats:italic>\n \u00a0<\u00a00.05) and in vivo (\n n<\/jats:italic>\n \u00a0=\u00a06,\n P<\/jats:italic>\n \u00a0<\u00a00.05). Specific silencing of\n miR\u2010690<\/jats:italic>\n in the muscle can promote satellite cell differentiation (\n n<\/jats:italic>\n \u00a0=\u00a06,\n P<\/jats:italic>\n \u00a0<\u00a00.001) and alleviate muscle atrophy in aged mice (\n n<\/jats:italic>\n \u00a0=\u00a06,\n P<\/jats:italic>\n \u00a0<\u00a00.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our study demonstrated that atrophic muscle fibre\u2010derived sEV\n miR\u2010690<\/jats:italic>\n may inhibit satellite cell differentiation by targeting myocyte enhancer factor 2 during ageing.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.13106","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T02:23:14Z","timestamp":1665714194000},"page":"3163-3180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Atrophic skeletal muscle fibre\u2010derived small extracellular vesicle miR\u2010690 inhibits satellite cell differentiation during ageing"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaoyan","family":"Shao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University & Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing Jiangsu China"},{"name":"Jiangsu Key Laboratory of Molecular Medicine, Medical School Nanjing University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Gong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University & Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing Jiangsu 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Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing Jiangsu China"},{"name":"Jiangsu Key Laboratory of Molecular Medicine, Medical School Nanjing University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianshu","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University & Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing Jiangsu China"},{"name":"Jiangsu Key Laboratory of Molecular Medicine, Medical School Nanjing University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdurahman","family":"Mahmut","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University & Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing Jiangsu China"},{"name":"Jiangsu Key Laboratory of Molecular Medicine, Medical School Nanjing University Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghui","family":"Qin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University & Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing Jiangsu China"},{"name":"Jiangsu Key Laboratory of Molecular Medicine, Medical School Nanjing University Nanjing Jiangsu 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afy106"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afy169"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169548"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300182"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00408.2005"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00066-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2007.12.012"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4116"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12584"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00042"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01131-0"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.10.021"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2017.09.006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6977"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3118"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.12.010"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084153"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13105-9"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.005"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13107"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2012.00260"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13013"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2011.76.010652"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03260"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103607"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00929"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.26808"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-016-0073-y"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.12.019"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.008367"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.179663.111"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2495"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1401732111"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3710"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12397"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01187-07"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02156-4"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01715-4"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-1558"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11071119"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12899"}],"container-title":["Journal of Cachexia, Sarcopenia and 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