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Muscle RANK is a key regulator of Ca 2+ storage, SERCA activity, and function of fast-twitch skeletal muscles
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 deleti...
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Published in: | American Journal of Physiology: Cell Physiology 2016-04, Vol.310 (8), p.C663-C672 |
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Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 0363-6143 1522-1563 |
DOI: | 10.1152/ajpcell.00285.2015 |