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We wanted to determine the role of TGF\u2010\u03b2\u2010induced ECM remodelling in dystrophic muscle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We experimentally induced the pathological hallmarks of severe muscular dystrophy by mechanically overloading the <jats:italic>plantaris<\/jats:italic> muscle in mice. Furthermore, we determined the role of TGF\u2010\u03b2 signalling on dystrophic tissue modulation and on muscle function by (i) overloading myostatin knockout (<jats:italic>Mstn<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>) mice and (ii) by additional pharmacological TGF\u2010\u03b2 inhibition <jats:italic>via<\/jats:italic> halofuginone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Transcriptome analysis of overloaded muscles revealed upregulation predominantly of genes associated with ECM, inflammation and metalloproteinase activity. Histology revealed in wild\u2010type mice signs of severe muscular dystrophy including myofibres with large variation in size and internalized myonuclei, as well as increased ECM deposition. At the same time, muscle weight had increased by 208% and muscle force by 234%. Myostatin deficiency blunted the effect of overload on muscle mass (59% increase) and force (76% increase), while having no effect on ECM deposition. Concomitant treatment with halofuginone blunted overload\u2010induced muscle hypertrophy and muscle force increase, while reducing ECM deposition and increasing myofibre size.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ECM remodelling is associated with an increase in muscle mass and force in overload\u2010modelled dystrophic muscle. Lack of myostatin is not advantageous and inhibition of ECM deposition by halofuginone is disadvantageous for muscle plasticity in response to stimuli that induce dystrophic muscle.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12655","type":"journal-article","created":{"date-parts":[[2020,8,9]],"date-time":"2020-08-09T20:56:35Z","timestamp":1597006595000},"page":"218-235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Extracellular matrix remodelling is associated with muscle force increase in overloaded mouse <i>plantaris<\/i> muscle"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4903-6384","authenticated-orcid":false,"given":"A.","family":"Stantzou","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay UVSQ Inserm END\u2010ICAP Versailles 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Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Gallen","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay UVSQ Inserm END\u2010ICAP Versailles France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Grassin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay UVSQ Inserm END\u2010ICAP Versailles France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ferry","sequence":"additional","affiliation":[{"name":"Center for Research in Myology Pierre et Marie Curie University Paris Sorbonne INSERM UMRS974 CNRS FRE3617 Paris France"},{"name":"Universit\u00e9 Paris Descartes Sorbonne Paris Cit\u00e9 Paris 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