The nutritional level of
vitamin D may affect musculoskeletal health. We have reported that
vitamin D is a pivotal protector against tissue
injuries by suppressing local renin-angiotensin system (RAS). This study aimed to explore the role of the
vitamin D receptor (VDR) in the protection against
muscle atrophy and the underlying mechanism. A cross-sectional study on participants (n = 1034) in Shanghai (China) was performed to analyze the association between
vitamin D level and the risk of low muscle strength as well as to detect the circulating level of
angiotensin II (Ang II). In animal studies,
dexamethasone (Dex) was applied to induce
muscle atrophy in wild-type (WT) and VDR-null mice, and the mice with the induction of
muscle atrophy were treated with
calcitriol for 10 days. The skeletal muscle cell line C2C12 and the muscle satellite cells were applied in in vitro studies. The increased risk of low muscle strength was correlated to a lower level of
vitamin D (adjusted odds ratio [OR] 0.58) accompanied by an elevation in serum Ang II level. Ang II impaired the myogenic differentiation of C2C12 myoblasts as illustrated by the decrease in the area of myotubes and the downregulation of myogenic factors (
myosin heavy chain [MHC] and myogenic differentiation
factor D [MyoD]). The phenotype of
muscle atrophy induced by Dex and Ang II was aggravated by VDR ablation in mice and in muscle satellite cells, respectively, and mediated by RAS and its downstream
phosphatidylinositol 3-kinase/
protein kinase B/forkhead box O1 (PI3K/Akt/FOXO1) signaling.
Calcitriol treatment exhibited beneficial effects on muscle function as demonstrated by the increased weight-loaded swimming time, grip strength, and fiber area, and improved fiber type composition via regulating
ubiquitin ligases and their substrates MHC and MyoD through suppressing
renin/Ang II axis. Taken together, VDR protects against skeletal muscle
atrophy by suppressing RAS.
Vitamin D could be a potential agent for the prevention and treatment of skeletal muscle
atrophy. © 2021 American Society for Bone and
Mineral Research (ASBMR).