Regulation of vitamin D system in skeletal muscle and resident myogenic stem cell during development, maturation, and ageing

Skeletal muscle exhibits enormous plasticity throughout life, however, less is known regarding how the stages of growth regulate its local vitamin D system. Herein, we investigated serum 25(OH)D(3) and Ca(2+) levels along with the vitamin D system in skeletal muscle and resident myogenic stem cells of male C57BL/6 mice during development, maturation, and ageing. Compared with development, significant increases in vitamin D receptor (VDR) protein expression in mature and aged muscles were associated with increased serum 25(OH)D(3) and centronucleated fibres, respectively. The substantial increase in VDR protein expression in aged muscle was also related to reduced downstream mTOR signalling protein expression which was more pronounced in fast-glycolytic compared to slow-oxidative muscles. Intriguingly, serum Ca(2+) and vitamin D-metabolising enzyme (CYP27B1 and CYP24A1) levels in skeletal muscle were not different across age. In primary cell culture, nuclear VDR protein was expressed in undifferentiated skeletal muscle stem cells (SMSC) after 1α,25(OH)(2)D(3) treatment. Additionally, a diminished response to 1α,25(OH)(2)D(3) was observed with age as there was a rapid commitment of SMSC towards differentiation under growth-stimulating conditions. Collectively, understanding the local vitamin D system in skeletal muscle could help develop effective interventions for vitamin D supplementation to improve skeletal muscle mass and function during ageing.