Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles

作者：Dufresne Sebastien S; Dumont Nicolas A; Boulanger Piette Antoine; Fajardo Val A; Gamu Daniel; Kake Guena Sandrine Aurelie; David Rares Ovidiu; Bouchard Patrice; Lavergne Eliane; Penninger Josef M; Pape Paul C; Tupling A Russell; Frenette Jerome^*

来源：American Journal of Physiology - Cell Physiology, 2016, 310(8): C663-C672.

DOI：10.1152/ajpcell.00285.2015

• receptor-activator of nuclear factor-kappa B
• sarco(endo) plasmic reticulum Ca2+-ATPase

Receptor-activator of nuclear factor-kappa B (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 Ca2+ sensor, and altered activity of the sarco(endo) plasmic reticulum Ca2+-ATPase (SERCA) modulating Ca2+ 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 Ca2+ storage and SERCA activity, ultimately affecting denervated skeletal muscle function.

• 出版日期2016-4-15