Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Advanced Therapy for Musculoskeletal Disorders II, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Sci Rep. 2020 Jul 22;10(1):12242. doi: 10.1038/s41598-020-69021-y.
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.
维生素 D 缺乏是肌肉减少症发展的公认危险因素，但这一结果的机制尚不清楚。在这里，我们表明，低维生素 D 状态会使小鼠的固定性肌肉萎缩恶化。与对照组相比，全身缺乏维生素 D 受体 (VDR) 的小鼠在四肢固定后出现更严重的肌肉萎缩。此外，与骨骼肌特异性 VDR 缺陷型小鼠相比，神经嵴特异性 VDR 缺陷型小鼠的固定性肌肉萎缩更为严重。与对照组相比，VDR 缺陷型小鼠固定肌肉中的 TNFα 表达显著升高，而在神经嵴特异性而非肌肉特异性 VDR 缺陷型小鼠中则显著升高。此外，在低维生素 D 小鼠中，肢体固定引起的肌肉萎缩在 TNFα 缺陷型小鼠中显著受到抑制。我们得出结论，维生素 D 通过神经嵴衍生细胞中表达的 VDR 拮抗固定性肌肉萎缩。
