Myogenic, genomic and non-genomic influences of the vitamin D axis in skeletal muscle.

Abstract

Despite vitamin D-deficiency clinically presenting with myopathy, muscle weakness and atrophy, the mechanisms by which vitamin D exerts its homeostatic effects upon skeletal muscle remain to be fully established. Recent studies have shown that the receptor by which 1α,25-dihydroxyvitamin D3 (1,25[OH]2 D3 ) exerts its biological actions (ie, the vitamin D receptor, VDR) elicits both genomic and non-genomic effects upon skeletal muscle. The controversy surrounding skeletal muscle VDR mRNA/protein expression in post-natal muscle has been allayed by myriad recent studies, while dynamic expression of VDR throughout myogenesis, and association of higher VDR levels during muscle regeneration/immature muscle cells, suggests a role in myogenesis and perhaps an enrichment of VDR in satellite cells. Accordingly, in vitro studies have demonstrated 1,25(OH)2 D3 is anti-proliferative in myoblasts, yet pro-differentiation in latter stages of myogenesis. These effects involve modulation of gene expression (VDR as a transcriptional co-activator controls ~3% of the genome) and post-genomic intracellular signalling for example, via c-Src and alterations to intramuscular calcium homeostasis and proteostasis. The aim of this review is to consider the biomolecular role for the vitamin D/VDR axis in myogenesis, while also exploring global evidence for genomic and non-genomic mechanisms of action for 1,25(OH)2 D3 /VDR.