Vitamin D protects against immobilization-induced muscle atrophy via neural crest-derived cells in mice

Abstract

Vitamin D deficiency is a recognized risk factor for sarcopenia development, but mechanisms underlying this outcome are unclear. Here, we show that low vitamin D status worsens immobilization-induced muscle atrophy in mice. Mice globally lacking vitamin D receptor (VDR) exhibited more severe muscle atrophy following limb immobilization than controls. Moreover, immobilization-induced muscle atrophy was worse in neural crest-specific than in skeletal muscle-specific VDR-deficient mice. Tnfα expression was significantly higher in immobilized muscle of VDR-deficient relative to control mice, and was significantly elevated in neural crest-specific but not muscle-specific VDR-deficient mice. Furthermore, muscle atrophy induced by limb immobilization in low vitamin D mice was significantly inhibited in Tnfα-deficient mice. We conclude that vitamin D antagonizes immobilization-induced muscle atrophy via VDR expressed in neural crest-derived cells.

Vitamin D Supplementation and Impact on Skeletal Muscle Function in Cell and Animal Models and an Aging Population: What Do We Know So Far?

“…In animal studies ( Table 2 ), VitD deficiency has led to detrimental effects in skeletal muscle, mainly resulting in muscle atrophy [ 43 , 44 , 48 ]. Nakamura et al have demonstrated that low VitD status resulted in worse mobilization and induced muscle atrophy in mice [ 44 ] ( Table 2 ). The last authors have concluded that maintaining sufficient levels of VitD is likely to prevent deterioration and skeletal muscle atrophy [ 44 ].…”

“…Nakamura et al have demonstrated that low VitD status resulted in worse mobilization and induced muscle atrophy in mice [ 44 ] ( Table 2 ). The last authors have concluded that maintaining sufficient levels of VitD is likely to prevent deterioration and skeletal muscle atrophy [ 44 ]. In accordance with this study, Gifondorwa et al have reported that a VitD deficient diet resulted in detrimental changes in the structure and function of the neuromuscular junction [ 43 ].…”

Mouse models of sarcopenia: classification and evaluation

“…Some studies even used fixation combined with hindlimb unloading to exaggerate the muscle loss induced by no load to build a mouse model of sarcopenia 124 . The immobilization time ranged from 1 to 3 weeks, depending on the researchers' experimental design 120,122–124 . Compared with traditional plaster fixation, surgical staplers and other immobilization models are simple and can be carried out in a few seconds, which makes it possible to carry out high‐throughput analysis with high reproducibility.…”

Renal Rehabilitation: Exercise Intervention and Nutritional Support in Dialysis Patients

“…Vitamin D deficiency is common phenomenon in CKD patients. It is reported that maintaining appropriate vitamin D levels is crucial to protect muscle from significant atrophy [ 70 ]. Moreover, iron deficiency in skeletal muscle metabolism is strongly associated with lower exercise tolerance independent from anemia, since it is an essential component of oxygen uptake, transport, storage, erythropoiesis, the mitochondrial electron transport chain, and antioxidant enzymes [ 71 ].…”