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It is important for tendon maturation, running performance and has key implications for the resident tendon stem\/progenitor cells (TSPCs). However, its exact functions during the tendon repair process still remain elusive. Here, we established an Achilles tendon injury model in a <jats:italic>Tnmd<\/jats:italic> knockout (<jats:italic>Tnmd<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) mouse line. Detailed analyses showed not only a very different scar organization with a clearly reduced cell proliferation and expression of certain tendon-related genes, but also increased cell apoptosis, adipocyte and blood vessel accumulation in the early phase of tendon healing compared with their wild-type (WT) littermates. In addition, <jats:italic>Tnmd<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> tendon scar tissue contained augmented matrix deposition of biglycan, cartilage oligomeric matrix protein (Comp) and fibronectin, altered macrophage profile and reduced numbers of CD146-positive cells. <jats:italic>In vitro<\/jats:italic> analysis revealed that <jats:italic>Tnmd<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> TSPCs exhibited significantly reduced migration and proliferation potential compared with that of WT TSPCs. Furthermore, <jats:italic>Tnmd<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> TSPCs had accelerated adipogenic differentiation accompanied with significantly increased peroxisome proliferator-activated receptor gamma (<jats:italic>Ppar\u03b3<\/jats:italic>) and lipoprotein lipase (<jats:italic>Lpl<\/jats:italic>) mRNA levels. Thus, our results demonstrate that Tnmd is required for prevention of adipocyte accumulation and fibrovascular scar formation during early tendon healing.<\/jats:p>","DOI":"10.1038\/cddis.2017.510","type":"journal-article","created":{"date-parts":[[2017,10,12]],"date-time":"2017-10-12T12:43:02Z","timestamp":1507812182000},"page":"e3116-e3116","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["Tenomodulin is essential for prevention of adipocyte accumulation and fibrovascular scar formation during early tendon healing"],"prefix":"10.1038","volume":"8","author":[{"given":"Dasheng","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Alberton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel Delgado","family":"Caceres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Volkmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schieker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7588-1290","authenticated-orcid":false,"given":"Denitsa","family":"Docheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,10,12]]},"reference":[{"key":"BFcddis2017510_CR1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/nrrheum.2015.26","volume":"11","author":"G Nourissat","year":"2015","unstructured":"Nourissat G, Berenbaum F, Duprez D . 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