{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:21:43Z","timestamp":1787008903566,"version":"build-2736575974"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T00:00:00Z","timestamp":1560124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2016-05845"],"award-info":[{"award-number":["RGPIN-2016-05845"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Duchenne muscular dystrophy (DMD) is the most severe form of muscular dystrophy which leads to progressive muscle degeneration and inflammation. The receptor activator of nuclear factor NF-\u03baB ligand (RANKL) and its receptor (RANK), which are expressed in bone and skeletal and cardiac muscles, form a signaling network upstream from nuclear factor-kappa B (NF-\u03baB). We thus hypothesized that prolonged silencing RANKL\/RANK signaling would significantly improve DMD. We showed that RANK and RANKL protein levels were increased in the microenvironment of myofibers of 5-month-old utrophin haploinsufficient mdx (mdx\/utrn+\/\u2212) mice and that a 4\u00a0mg\/kg dose of anti-RANKL antibody every 3 d for 28\u00a0days is optimal and more effective than 1\u00a0mg\/kg every 3 d for improving the ex vivo maximum specific force (sP0) of dystrophic EDL muscles from mdx\/utrn+\/\u2212 mice. This functional improvement was associated with a reduction in muscle edema, damage, and fibrosis and a marked reduction in serum CK levels. The anti-RANKL treatment inhibited the NF-\u03baB pathway, increased the proportion of anti-inflammatory and non-cytotoxic M2 macrophages, and reduced the number of centrally-nucleated myofibers and the frequency of small myofibers, suggesting that anti-RANKL inhibits the cycle of degeneration\/regeneration in dystrophic mice. A three-point bending test showed that a 28-d anti-RANKL treatment increases the mechanical properties of bone in mdx\/utrn+\/\u2212 dystrophic mice. In conclusion, the anti-RANKL treatment protected against skeletal muscle dysfunctions while enhancing bone mechanical properties, filling two needs with one deed in the context of muscular dystrophy.<\/jats:p>","DOI":"10.1093\/hmg\/ddz124","type":"journal-article","created":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T15:13:17Z","timestamp":1559833997000},"page":"3101-3112","source":"Crossref","is-referenced-by-count":55,"title":["An anti-RANKL treatment reduces muscle inflammation and dysfunction and strengthens bone in dystrophic mice"],"prefix":"10.1093","volume":"28","author":[{"given":"Dounia","family":"Hamoudi","sequence":"first","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec, Centre de Recherche du Centre Hospitalier de l\u2019 Universit\u00e9 Laval (CHUQ-CHUL), Universit\u00e9 Laval, Quebec City, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Marcadet","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec, Centre de Recherche du Centre Hospitalier de l\u2019 Universit\u00e9 Laval (CHUQ-CHUL), Universit\u00e9 Laval, Quebec City, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Piette Boulanger","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec, Centre de Recherche du Centre Hospitalier de l\u2019 Universit\u00e9 Laval (CHUQ-CHUL), Universit\u00e9 Laval, Quebec City, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Yagita","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Juntendo University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zineb","family":"Bouredji","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec, Centre de Recherche du Centre Hospitalier de l\u2019 Universit\u00e9 Laval (CHUQ-CHUL), Universit\u00e9 Laval, Quebec City, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anteneh","family":"Argaw","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec, Centre de Recherche du Centre Hospitalier de l\u2019 Universit\u00e9 Laval (CHUQ-CHUL), Universit\u00e9 Laval, Quebec City, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Frenette","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec, Centre de Recherche du Centre Hospitalier de l\u2019 Universit\u00e9 Laval (CHUQ-CHUL), Universit\u00e9 Laval, Quebec City, QC, Canada"},{"name":"D\u00e9partement de R\u00e9adaptation, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Laval, Quebec City, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,10]]},"reference":[{"key":"2019091103283107800_ref1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/humu.22758","article-title":"The TREAT-NMD DMD global database: analysis of more than 7,000 Duchenne muscular dystrophy mutations","volume":"36","author":"Bladen","year":"2015","journal-title":"Hum. 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