{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:37:08Z","timestamp":1788953828665,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"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":["82304642"],"award-info":[{"award-number":["82304642"]}],"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":["81773827"],"award-info":[{"award-number":["81773827"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20210430"],"award-info":[{"award-number":["BK20210430"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2020M681786"],"award-info":[{"award-number":["2020M681786"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2022YFC2703600"],"award-info":[{"award-number":["2022YFC2703600"]}],"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":[[2025,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Oestrogen receptor alpha (ER\u03b1) plays an important role in maintaining mitochondrial function and regulating metabolism in skeletal muscle. However, its alterations and potential mechanisms in Duchenne muscular dystrophy (DMD) remain incompletely understood. In this study, we demonstrated the protective role of ER\u03b1 in myocyte for skeletal muscle regeneration in\n mdx<\/jats:italic>\n mice and explored the therapeutic effects of oestrogen receptor modulators on DMD.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n DMD patients' biopsies were obtained for histological analysis to explore the expression of ER\u03b1. The phenotype of muscle was analysed by histology and molecular biology. The therapeutical effect of different oestrogen receptor modulators was examined in\n mdx<\/jats:italic>\n mice treated with fulvestrant (FVT, 20\u2009mg\/kg once a week) or oestradiol (E2, 1\u2009mg\/kg per day) for 4\u2009weeks. The protective effect of ER\u03b1 was performed on\n mdx<\/jats:italic>\n mice after conditional knockout of ER\u03b1 in skeletal muscle (ER\u03b1\n mKO<\/jats:sup>\n mdx<\/jats:italic>\n mice). Evidence of activation of ER\u03b1\/oestrogen\u2010related receptor alpha (ERR\u03b1)\/myogenic differentiation 1 (MyoD) signalling pathway was inspected in the primary myoblasts isolated from mice, and C2C12 cells received intervention with E2\/FVT\/\n Esr1<\/jats:italic>\n \u2010siRNA\/\n Esrra<\/jats:italic>\n overexpression plasmid.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The ER\u03b1 expression was increased in DMD patients' triceps (\n p<\/jats:italic>\n \u2009<\u20090.05) and\n mdx<\/jats:italic>\n mice muscles (\n p<\/jats:italic>\n \u2009<\u20090.05). FVT reduced ER\u03b1 levels in the\n mdx<\/jats:italic>\n mice muscles (\n p<\/jats:italic>\n \u2009<\u20090.01) but had no significant effect on skeletal muscle regeneration on\n mdx<\/jats:italic>\n mice. Compared with\n mdx<\/jats:italic>\n mice, E2 reduced the levels of creatine kinase (CK) and lactic dehydrogenase (LDH) (\n p<\/jats:italic>\n \u2009<\u20090.001) in serum, enhanced skeletal muscle function, alleviated skeletal muscle atrophy and fibre loss and upregulated the expression of ER\u03b1 in GAS (\n p<\/jats:italic>\n \u2009<\u20090.001) and TA (\n p<\/jats:italic>\n \u2009<\u20090.05). The myogenic factors such as myosin heavy chain (MyHC,\n p<\/jats:italic>\n \u2009<\u20090.001), myogenin (MyoG,\n p<\/jats:italic>\n \u2009<\u20090.05), MyoD (\n p<\/jats:italic>\n \u2009<\u20090.05) and ERR\u03b1 (\n p<\/jats:italic>\n \u2009<\u20090.001) were increased in\n mdx<\/jats:italic>\n mice GAS with E2. But E2 had no effect on ER\u03b1\n mKO<\/jats:sup>\n mdx<\/jats:italic>\n mice. The primary myoblasts and C2C12 were treated with E2 displayed an increased\u2010on myocyte fusion index (\n p<\/jats:italic>\n \u2009<\u20090.05), ER\u03b1 MyoD and ERR\u03b1 expressions (\n p<\/jats:italic>\n \u2009<\u20090.05). The myocytes' fusion index (\n p<\/jats:italic>\n \u2009<\u20090.05) and ER\u03b1, MyoD and ERR\u03b1 expression (\n p<\/jats:italic>\n \u2009<\u20090.05) were decreased in si\u2010\n Esr1<\/jats:italic>\n \u2010transfected C2C12 cells and increased in OE\u2010\n Esrra<\/jats:italic>\n \u2010transfected C2C12 cells.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n We demonstrated that ER\u03b1 in myocyte exerted a protective effect on skeletal muscle regeneration in DMD patients and\n mdx<\/jats:italic>\n mice through the ER\u03b1\u2010ERR\u03b1\u2010MyoD pathway, which has potential implications for DMD therapy strategies.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.13807","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T02:36:24Z","timestamp":1745462184000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Oestrogen Receptor Alpha in Myocyte Maintains Muscle Regeneration in Duchenne Muscular Dystrophy"],"prefix":"10.1002","volume":"16","author":[{"given":"Xiaofei","family":"Huang","sequence":"first","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Li","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huna","family":"Wang","sequence":"additional","affiliation":[{"name":"New Drug Screening and Pharmacodynamics Evaluation Center China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology Children's Hospital of Fudan University Shanghai 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P.BraithwaiteandY.Al Khalili \u201cPhysiology Muscle Myocyte \u201d in Treasure Island (FL) ineligible companies. Disclosure: Yasir Al Khalili declares no relevant financial relationships with ineligible companies (2025)."},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.2c00720"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2023.101670"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0249472"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12581"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192571199"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0294236"},{"key":"e_1_2_8_30_1","first-page":"764","article-title":"Ablation of Skeletal Muscle Estrogen Receptor Alpha Impairs Contractility in Male Mice","volume":"2024","author":"Sullivan B. 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