Mechanisms of vitamin D action in skeletal muscle

Abstract

Vitamin D receptor expression and associated function have been reported in various muscle models, including C2C12, L6 cell lines and primary human skeletal muscle cells. It is believed that 1,25-hydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, has a direct regulatory role in skeletal muscle function, where it participates in myogenesis, cell proliferation, differentiation, regulation of protein synthesis and mitochondrial metabolism through activation of various cellular signalling cascades, including the mitogen-activated protein kinase pathway(s). It has also been suggested that 1,25(OH)2D3 and its associated receptor have genomic targets, resulting in regulation of gene expression, as well as non-genomic functions that can alter cellular behaviour through binding and modification of targets not directly associated with transcriptional regulation. The molecular mechanisms of vitamin D signalling, however, have not been fully clarified. Vitamin D inadequacy or deficiency is associated with muscle fibre atrophy, increased risk of chronic musculoskeletal pain, sarcopenia and associated falls, and may also decrease RMR. The main purpose of the present review is to describe the molecular role of vitamin D in skeletal muscle tissue function and metabolism, specifically in relation to proliferation, differentiation and protein synthesis processes. In addition, the present review also includes discussion of possible genomic and non-genomic pathways of vitamin D action.

Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3

“…Vitamin D can regulate a variety of important pathways [34][35][36][37] . Among these, the NF-κB pathway plays an important role in the regulation of cisplatin sensitivity.…”

Vitamin D and Endothelial Function

“…Similarly, the positive association between plasma vitamin D concentrations and GSH bioavailability were observed in humans with type 2 diabetes (T2D) [88]. In addition, vitamin D improved antioxidative capacity through the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) in diabetic mice [89], a major antioxidant system that regulates the expression of various ROS detoxifying and antioxidant enzymes including NF-kB, hemeoxygenase-1, ubiquitin/PKC-ζ-interacting protein A170, peroxiredoxin 1, the heavy and light chain of ferritin, catalase, and thioredoxin [90][91][92][93][94][95] (Figure 3). The antioxidative potential of vitamin D has been proposed in avascular cells.…”

Nutritional Supplements to Support Resistance Exercise in Countering the Sarcopenia of Aging

“…Vitamin D 2 , obtained in dietary sources (i.e., salmon or mushrooms), undergoes the same hydroxylation process prior to entering circulation [ 146 , 147 ]. The precise molecular machinery involved in vitamin D-dependent skeletal muscle remodeling remains elusive, however vitamin D and the vitamin D receptor may play a role in modulating satellite cell activity, protein synthesis, mitochondrial metabolism, as well as energy production through various protein pathways (i.e., akt-mTORC1, myostatin, forkhead box O3) that play a role in the maintenance of skeletal muscle mass and function [ 148 , 149 ].…”