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Nutr Res Rev. 2019 Jun 17:1-13. doi: 10.1017/S0954422419000064. [Epub ahead of print]

Mechanisms of vitamin D action in skeletal muscle.

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School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University,Perth, WA 6102,Australia.


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.


1; 25(OH)D 25-hydroxyvitamin D; Akt protein kinase B; IGF insulin-like growth factor; MAPK mitogen-activated protein kinase; MEF myocyte enhancer factor; MRF myogenic regulatory factor; MYOG myogenin; Myf5 myogenic factor 5; MyoD myoblast determination protein; PKB protein kinase B; RCT randomised controlled trial; TGF-β transforming growth factor β; VDR vitamin D receptor; mTOR mammalian target of rapamycin; 25(OH)2D3 1; 25-hydroxyvitamin D3 ; Calcitriol; Mitochondria; Muscle; Myogenesis; Protein synthesis


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