{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:24:17Z","timestamp":1779931457408,"version":"3.53.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:italic>Carbohydrate sulfotransferase 14<\/jats:italic> (<jats:italic>CHST14<\/jats:italic>) encodes dermatan 4-<jats:italic>O<\/jats:italic>-sulfotransferase 1, a critical enzyme for dermatan sulfate (DS) biosynthesis. Musculocontractural Ehlers-Danlos syndrome (mcEDS) is associated with biallelic pathogenic variants of <jats:italic>CHST14<\/jats:italic> and is characterized by malformations and manifestations related to progressive connective tissue fragility. We identified myopathy phenotypes in <jats:italic>Chst14<\/jats:italic>-deficient mice using an mcEDS model. Decorin is a proteoglycan harboring a single glycosaminoglycan chain containing mainly DS, which are replaced with chondroitin sulfate (CS) in mcEDS patients with CHST14 deficiency. We studied the function of decorin in the skeletal muscle of <jats:italic>Chst14<\/jats:italic>-deficient mice because decorin is important for collagen-fibril assembly and has a myokine role in promoting muscle growth. Although decorin was present in the muscle perimysium of wild-type (<jats:italic>Chst14<jats:sup>+\/+<\/jats:sup><\/jats:italic>) mice, decorin was distributed in the muscle perimysium as well as in the endomysium of <jats:italic>Chst14<jats:sup>\u2013\/\u2013<\/jats:sup><\/jats:italic> mice. <jats:italic>Chst14<jats:sup>\u2013\/\u2013<\/jats:sup><\/jats:italic> mice had small muscle fibers within the spread interstitium; however, histopathological findings indicated milder myopathy in <jats:italic>Chst14<jats:sup>\u2013\/\u2013<\/jats:sup><\/jats:italic> mice. Myostatin, a negative regulator of protein synthesis in the muscle, was upregulated in <jats:italic>Chst14<jats:sup>\u2013\/\u2013<\/jats:sup><\/jats:italic> mice. In the muscle of <jats:italic>Chst14<jats:sup>\u2013\/\u2013<\/jats:sup><\/jats:italic> mice, decorin was downregulated compared to that in <jats:italic>Chst14<jats:sup>+\/+<\/jats:sup><\/jats:italic> mice. <jats:italic>Chst14<jats:sup>\u2013\/\u2013<\/jats:sup><\/jats:italic> mice showed altered cytokine\/chemokine balance and increased fibrosis, suggesting low myogenic activity in DS-deficient muscle. Therefore, DS deficiency in mcEDS causes pathological localization and functional abnormalities of decorin, which causes disturbances in skeletal muscle myogenesis.<\/jats:p>","DOI":"10.3389\/fcell.2021.695021","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:46:38Z","timestamp":1634085998000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Myopathy Associated With Dermatan Sulfate-Deficient Decorin and Myostatin in Musculocontractural Ehlers-Danlos Syndrome: A Mouse Model Investigation"],"prefix":"10.3389","volume":"9","author":[{"given":"Yuko","family":"Nitahara-Kasahara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Posadas-Herrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Mizumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aki","family":"Nakamura-Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko U.","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayoshi","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin\u2019ichi","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Kosho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/s1359-6101(02)00020-5","article-title":"The balance between IL-1 and IL-1Ra in disease.","volume":"13","author":"Arend","year":"2002","journal-title":"Cytokine Growth Factor Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1002\/ajmg.c.31550","article-title":"The Ehlers-Danlos syndromes, rare types.","volume":"175","author":"Brady","year":"2017","journal-title":"Am. 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