title: Physiological role of receptor activator nuclear factor-kB (RANK) in denervation-induced muscle atrophy and dysfunction.
abstract: The bone remodeling and homeostasis are mainly controlled by the receptor-activator of nuclear factor kB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin (OPG) pathway. While there is a strong association between osteoporosis and skeletal muscle dysfunction, the functional relevance of a particular biological pathway that synchronously regulates bone and skeletal muscle physiopathology remains elusive. Our recent article published in the American Journal of Physiology (Cell Physiology) showed that RANK is also expressed in fully differentiated C2C12 myotubes and skeletal muscles. We used the Cre-Lox approach to inactivate muscle RANK (RANKmko) and showed that RANK deletion preserves the force of denervated fast-twitch EDL muscles. However, RANK deletion had no positive impact on slow-twitch Sol muscles. In addition, denervating RANKmkoEDL muscles induced an increase in the total calcium concentration ([CaT]), which was associated with a surprising decrease in SERCA activity. Interestingly, the levels of STIM-1, which mediates Ca2+influx following the depletion of SR Ca2+stores, were markedly higher in denervated RANKmkoEDL muscles. We speculated that extracellular Ca2+influx mediated by STIM-1 may be important for the increase in [CaT] and the gain of force in denervated RANKmkoEDL muscles. Overall, these findings showed for the first time that the RANKL/RANK interaction plays a role in denervation-induced muscle atrophy and dysfunction.
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval (CHUQ-CRCHUL), Université Laval, Quebec City, Quebec, G1V 4G2, 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 (CHUQ-CRCHUL), Université Laval, Quebec City, Quebec, G1V 4G2, Canada.
authors.forename: Antoine
authors.initials: A
authors.lastname: Boulanger-Piette
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval (CHUQ-CRCHUL), Université Laval, Quebec City, Quebec, G1V 4G2, Canada.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bossé
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval (CHUQ-CRCHUL), Université Laval, Quebec City, Quebec, G1V 4G2, Canada; Département de Réadaptation, Faculté de Médecine, Université Laval, Quebec City, Quebec, G1V 4G2, Canada.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Frenette
keywords: RANK; SERCA; calcium; skeletal muscle