Skeletal muscle predominantly controls basal metabolism by sustaining locomotive function. Development and maturations of skeletal muscle functions are affected by vitamin D endocrine function, as skeletal muscle-specific vitamin D receptor (VDR) knockout (KO) mice exhibited losing both muscle mass and performances. However, there were few studies verified the timing when vitamin D action becomes more dominant during myogenic development. Therefore, we investigated the maturations of skeletal muscle cells isolated from muscle-specific VDR KO mice.
Muscle-specific VDR KO mice was obtained by crossing skeletal muscle specific cre (creatine kinase cre) mice with VDR flox mice. A lack of VDR activity decreased locomotor performance measured by latticed infrared beam interruptions in the cage. As bone phenotype, the increased osteoclast activation appeared in these mice and resulted to the reduction of bone mass. Since bone metabolism participates to the muscle development, 1,25(OH)2D3-VDR activity in myoblast differentiation was assessed in cultured C2C12 cells in next step. During differentiation, the levels of VDR protein was higher in the early stage compared to the mature stage. To analyze ATP metabolism, protein expression of both CX43, a promoter of ATP transport, and ENPP1, an eliminator of ATP, were evaluated. The level of CX43 was decreased by cellular differentiation while ENPP1 was increased. Furthermore, the ratio of ATP/ADP at every 24-hour in cultured skeletal muscle was increased by 1,25(OH)2D3 stimulation in dose-dependent manner, the maximal effect was observed in 10-12M.
In conclusion, current study indicated that local VDR activity regulate the supply and the elimination of ATP in skeletal muscle, which is essential for muscle contraction, thereby contributes the physiological controls of locomotive function.