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Physiological role of receptor activator nuclear factor-κB (RANK) in denervation-induced muscle atrophy and dysfunction

Dufresne Sébastien S., Boulanger-Piette Antoine, Bossé Sabrina et Frenette Jérôme. (2016). Physiological role of receptor activator nuclear factor-κB (RANK) in denervation-induced muscle atrophy and dysfunction. Receptoirs & Clinical Investigation, 3, (2),

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URL officielle: http://dx.doi.org/10.14800/rci.1323

Résumé

The discovery of receptor-activator of nuclear factor kB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin (OPG) pathway led to a clearer understanding of bone remodeling and homeostasis. 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 RANKmko EDL 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 RANKmko EDL 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.

Type de document:Article publié dans une revue avec comité d'évaluation
Volume:3
Numéro:2
Version évaluée par les pairs:Oui
Date:2016
Sujets:Sciences de la santé
Sciences de la santé > Sciences de l'activité physique et réadaptation
Sciences de la santé > Sciences de l'activité physique et réadaptation > Physiothérapie
Département, module, service et unité de recherche:Départements et modules > Département des sciences de la santé > Unité d'enseignement en physiothérapie
Mots-clés:RANK, skeletal muscule, calcium, SERCA
Déposé le:21 sept. 2016 13:49
Dernière modification:25 nov. 2016 16:54
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