title: Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles.
abstract: Receptor-activator of nuclear factor-κB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 content, a Ca(2+)sensor, and altered activity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) modulating Ca(2+)storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus muscles. These data identify a novel role for RANK as a key regulator of Ca(2+)storage and SERCA activity, ultimately affecting denervated skeletal muscle function.
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Quebec City, Quebec, Canada;
authors.forename: Sébastien S
authors.initials: SS
authors.lastname: Dufresne
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Quebec City, Quebec, Canada;
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Dumont
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Quebec City, Quebec, Canada;
authors.forename: Antoine
authors.initials: A
authors.lastname: Boulanger-Piette
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada;
authors.forename: Val A
authors.initials: VA
authors.lastname: Fajardo
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada;
authors.forename: Daniel
authors.initials: D
authors.lastname: Gamu
authors.affiliation: Faculté de Médecine et des Sciences de la Santé, Département de Physiologie et Biophysique, Université de Sherbrooke, Sherbrooke, Québec, Canada;
authors.forename: Sandrine-Aurélie
authors.initials: SA
authors.lastname: Kake-Guena
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Quebec City, Quebec, Canada;
authors.forename: Rares Ovidiu
authors.initials: RO
authors.lastname: David
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Quebec City, Quebec, Canada;
authors.forename: Patrice
authors.initials: P
authors.lastname: Bouchard
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Quebec City, Quebec, Canada;
authors.forename: Éliane
authors.initials: É
authors.lastname: Lavergne
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria; and.
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.affiliation: Faculté de Médecine et des Sciences de la Santé, Département de Physiologie et Biophysique, Université de Sherbrooke, Sherbrooke, Québec, Canada;
authors.forename: Paul C
authors.initials: PC
authors.lastname: Pape
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada;
authors.forename: A Russell
authors.initials: AR
authors.lastname: Tupling
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Quebec City, Quebec, Canada; Faculté de Médecine, Département de Réadaptation, Université Laval, Quebec City, Quebec, Canada jerome.frenette@crchul.ulaval.ca.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Frenette
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D007537:Isometric Contraction / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*
chemical_list: D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium
keywords: receptor-activator of nuclear factor-κB; sarco(endo)plasmic reticulum Ca2+-ATPase
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