{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:54:23Z","timestamp":1792274063693,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"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":["82202654"],"award-info":[{"award-number":["82202654"]}],"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":["BK20230176"],"award-info":[{"award-number":["BK20230176"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20210715"],"award-info":[{"award-number":["BK20210715"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010038","name":"Earmarked Fund for China Agriculture Research System","doi-asserted-by":"publisher","award":["CARS\u201048"],"award-info":[{"award-number":["CARS\u201048"]}],"id":[{"id":"10.13039\/501100010038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["23NSFSC1804"],"award-info":[{"award-number":["23NSFSC1804"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2019YFA0802400"],"award-info":[{"award-number":["2019YFA0802400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701347"],"award-info":[{"award-number":["81701347"]}],"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":["31961133026"],"award-info":[{"award-number":["31961133026"]}],"id":[{"id":"10.13039\/501100001809","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":[[2025,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n Myostatin (MSTN), a transforming growth factor\u2010beta (TGF\u2010\u03b2) superfamily member, is an evolutionarily conserved negative regulator of skeletal muscle mass. Loss of MSTN commonly promotes augmentation in skeletal muscle mass in all animal species examined. Recent studies have demonstrated that circadian clock proteins play a critical role in the regulation of muscle mass and function, in part by modulating the expression of key muscle\u2010related genes. While myostatin has an important role in sustaining skeletal muscle protein turnover, it is unknown if circadian clock proteins regulate myostatin in a circadian pattern.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We analysed time\u2010course muscle samples from 16 animal species ranging from\n \n Caenorhabditis elegans<\/jats:italic>\n <\/jats:styled-content>\n to humans and examined the rhythmic expression pattern of\n Mstn<\/jats:italic>\n . We also used various circadian clock deficient models such as muscle\u2010specific\n Bmal1<\/jats:italic>\n knockout,\n Per1\/Per2<\/jats:italic>\n double knockout, genetic knockout of\n per0<\/jats:italic>\n and\n tim0<\/jats:italic>\n genes in fruit flies,\n clocka<\/jats:italic>\n gene in zebrafish and environmental perturbation.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Both mRNA and protein of MSTN exhibit rhythmic expression patterns in a variety of animal species ranging from\n \n Caenorhabditis elegans<\/jats:italic>\n <\/jats:styled-content>\n (\n C. elegans<\/jats:italic>\n ) to humans. The rhythmicity of\n Mstn<\/jats:italic>\n orthologs in muscle is evolutionarily conserved along with their sequence evolution in\n \n C. elegans<\/jats:italic>\n <\/jats:styled-content>\n ,\n \n Drosophila melanogaster<\/jats:italic>\n <\/jats:styled-content>\n ,\n Crustacea<\/jats:italic>\n , fish and mammals including mice (mRNA: amplitude\u2009=\u20090.188,\n p<\/jats:italic>\n \u2009<\u20090.0001; protein: amplitude\u2009=\u20090.255,\n p<\/jats:italic>\n \u2009<\u20090.05), goats, pigs and humans. In murine skeletal muscle, rhythmic expression of\n Mstn<\/jats:italic>\n is synchronized with the core circadian genes,\n Per2<\/jats:italic>\n . We then constructed a muscle\u2010specific\n Bmal1<\/jats:italic>\n knockout mouse model (\n Bmal1<\/jats:italic>\n \n MKO<\/jats:italic>\n <\/jats:sup>\n ). Notably,\n Bmal1<\/jats:italic>\n \n MKO<\/jats:italic>\n <\/jats:sup>\n mice had increased body weight (29.30\u2009\u00b1\u20090.85 vs. 32.16\u2009\u00b1\u20090.79,\n p<\/jats:italic>\n \u2009<\u20090.05) and lean mass (WT 23.33\u2009\u00b1\u20090.35 vs. 25.35\u2009\u00b1\u20090.45,\n p<\/jats:italic>\n \u2009<\u20090.01), while the difference in lean mass at 12\u2009weeks of age (~1.996\u2009g) closely matches the difference in total body weight (~ 2.000\u2009g). Muscle\u2010specific\n Bmal1<\/jats:italic>\n knockout reduced the mRNA and protein levels of\n mstn<\/jats:italic>\n \/MSTN by ~ 50%. In addition, disruption of the circadian clock by constant light or\n Per1\/Per2<\/jats:italic>\n double knockout also abolishes the rhythmicity of\n Mstn<\/jats:italic>\n . Similarly, genetic knockout of\n per0<\/jats:italic>\n and\n tim0<\/jats:italic>\n genes in fruit flies,\n clocka<\/jats:italic>\n gene in zebrafish (\n mstna<\/jats:italic>\n :\n p<\/jats:italic>\n \u2009<\u20090.01 vs.\n p<\/jats:italic>\n \u2009=\u20090.6397) and environmental perturbation (\n \n Aplodinotus grunniens<\/jats:italic>\n <\/jats:styled-content>\n ,\n mstn1<\/jats:italic>\n :\n p<\/jats:italic>\n \u2009<\u20090.0001 vs.\n p<\/jats:italic>\n \u2009=\u20090.04;\n mstn2<\/jats:italic>\n :\n p<\/jats:italic>\n \u2009<\u20090.05 vs.\n p<\/jats:italic>\n \u2009=\u20090.06) all alter\n Mstn<\/jats:italic>\n oscillation profoundly.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These findings reveal an evolutionarily conserved rhythmic expression pattern of\n Mstn<\/jats:italic>\n in skeletal muscles.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70130","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:17:23Z","timestamp":1764051443000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Myostatin Exhibits an Evolutionarily Conserved Circadian Pattern in Skeletal Muscles"],"prefix":"10.1002","volume":"16","author":[{"given":"Xiangpeng","family":"Liu","sequence":"first","affiliation":[{"name":"Cambridge\u2010Suda Genomic Resource Center Suzhou Medical College, Soochow University Suzhou China"},{"name":"Institues of Biomedical Sciences Inner Mongolia University Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyou","family":"Song","sequence":"additional","affiliation":[{"name":"Freshwater Fisheries Research Center Chinese Academy of Fishery Sciences Wuxi 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