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Though several reports have refuted these data, the\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    effects of GDF11 on skeletal muscle mass have not been addressed. Using\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    myoblast culture assays, we first demonstrate that GDF11 and Mstn have similar activities\/potencies on activating p\u2010SMAD2\/3 and induce comparable levels of differentiated myotube atrophy. We further demonstrate that adeno\u2010associated virus\u2010mediated systemic overexpression of GDF11 in C57BL\/6 mice results in substantial atrophy of skeletal and cardiac muscle, inducing a cachexic phenotype not seen in mice expressing similar levels of Mstn. Greater cardiac expression of\n                    <jats:italic>Tgfbr1<\/jats:italic>\n                    may explain this GDF11\u2010specific cardiac phenotype. These data indicate that bioactive GDF11 at supraphysiological levels cause wasting of both skeletal and cardiac muscle. Rather than a therapeutic agent, GDF11 should be viewed as a potential deleterious biomarker in muscle wasting diseases.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201607231","type":"journal-article","created":{"date-parts":[[2017,3,7]],"date-time":"2017-03-07T20:20:12Z","timestamp":1488918012000},"page":"531-544","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":115,"title":["Supraphysiological levels of GDF11 induce striated muscle atrophy"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2129-4047","authenticated-orcid":false,"given":"David W","family":"Hammers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Merscham\u2010Banda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer Ying","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Engst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J","family":"Hartman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6290-8853","authenticated-orcid":false,"given":"H Lee","family":"Sweeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,7]]},"reference":[{"key":"BFEMMM201607231_CR1","doi-asserted-by":"crossref","first-page":"e10230","DOI":"10.1371\/journal.pone.0010230","volume":"5","author":"LT Bish","year":"2010","unstructured":"Bish LT, Morine KJ, Sleeper MM, Sweeney HL (2010) Myostatin is upregulated following stress in an Erk\u2010dependent manner and negatively regulates cardiomyocyte growth in culture and in a mouse model. 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