{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T12:34:11Z","timestamp":1778589251020,"version":"3.51.4"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T00:00:00Z","timestamp":1685750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["CIHR- 168825"],"award-info":[{"award-number":["CIHR- 168825"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Institutes of Health Research","award":["RGPIN-2016-05845"],"award-info":[{"award-number":["RGPIN-2016-05845"]}]},{"name":"Canadian Institutes of Health Research","award":["CIHR- 168825"],"award-info":[{"award-number":["CIHR- 168825"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cardiomyopathy has become one of the leading causes of death in patients with Duchenne muscular dystrophy (DMD). We recently reported that the inhibition of the interaction between the receptor activator of nuclear factor \u03baB ligand (RANKL) and receptor activator of nuclear factor \u03baB (RANK) significantly improves muscle and bone functions in dystrophin-deficient mdx mice. RANKL and RANK are also expressed in cardiac muscle. Here, we investigate whether anti-RANKL treatment prevents cardiac hypertrophy and dysfunction in dystrophic mdx mice. Anti-RANKL treatment significantly reduced LV hypertrophy and heart mass, and maintained cardiac function in mdx mice. Anti-RANKL treatment also inhibited NF\u03baB and PI3K, two mediators implicated in cardiac hypertrophy. Furthermore, anti-RANKL treatment increased SERCA activity and the expression of RyR, FKBP12, and SERCA2a, leading possibly to an improved Ca2+ homeostasis in dystrophic hearts. Interestingly, preliminary post hoc analyses suggest that denosumab, a human anti-RANKL, reduced left ventricular hypertrophy in two patients with DMD. Taken together, our results indicate that anti-RANKL treatment prevents the worsening of cardiac hypertrophy in mdx mice and could potentially maintain cardiac function in teenage or adult patients with DMD.<\/jats:p>","DOI":"10.3390\/cells12111538","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T01:53:25Z","timestamp":1685930005000},"page":"1538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["RANKL Inhibition Reduces Cardiac Hypertrophy in mdx Mice and Possibly in Children with Duchenne Muscular Dystrophy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2746-3817","authenticated-orcid":false,"given":"Laetitia","family":"Marcadet","sequence":"first","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec, Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 Laval (CHUQ-CHUL), Axe Neurosciences, Universit\u00e9 Laval, Quebec City, QC G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma Sara","family":"Juracic","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, ON N2L 3G1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nasrin","family":"Khan","sequence":"additional","affiliation":[{"name":"The Ottawa Pediatric Bone Health Research Group, Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zineb","family":"Bouredji","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec, Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 Laval (CHUQ-CHUL), Axe Neurosciences, Universit\u00e9 Laval, Quebec City, QC G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Yagita","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine, Juntendo University, Tokyo 113-8421, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leanne M.","family":"Ward","sequence":"additional","affiliation":[{"name":"The Ottawa Pediatric Bone Health Research Group, Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada"},{"name":"The Department of Pediatrics, University of Ottawa, Ottawa, ON K1H 8L1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3895-6767","authenticated-orcid":false,"given":"A. Russell","family":"Tupling","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, ON N2L 3G1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anteneh","family":"Argaw","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec, Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 Laval (CHUQ-CHUL), Axe Neurosciences, Universit\u00e9 Laval, Quebec City, QC G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4308-9418","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Frenette","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Qu\u00e9bec, Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 Laval (CHUQ-CHUL), Axe Neurosciences, Universit\u00e9 Laval, Quebec City, QC G1V 4G2, Canada"},{"name":"Department of Rehabilitation, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pediatrneurol.2006.09.016","article-title":"Pathophysiology of Duchenne Muscular Dystrophy: Current Hypotheses","volume":"36","author":"Deconinck","year":"2007","journal-title":"Pediatr. 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