1,25(OH)2Vitamin D3 Stimulates Myogenic Differentiation by Inhibiting Cell Proliferation and Modulating the Expression of Promyogenic Growth Factors and Myostatin in C2C12 Skeletal Muscle Cells
1,25(OH)2Vitamin D3 Stimulates Myogenic Differentiation by Inhibiting Cell Proliferation and Modulating the Expression of Promyogenic Growth Factors and Myostatin in C2C12 Skeletal Muscle Cells
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DOI：
10.1210/en.2011-0159
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发表时间：
2011-08-01
期刊：
影响因子：
4.8
通讯作者：
Artaza, Jorge N.
中科院分区：
文献类型：
--
作者：
Garcia, Leah A.;King, Keisha K.;Artaza, Jorge N.
骨骼肌萎缩是与衰老、慢性病、癌症、肾透析和HIV/AIDS相关的重要公共卫生问题。1，25-二羟基维生素D（1，25-D3）是维生素D的活性形式，因其调节与骨发育和维持相关的钙和磷酸盐稳态以及其对靶器官（如肠、肾和甲状旁腺）的钙离子化作用而被广泛认可。新出现的证据表明，维生素D管理改善肌肉性能，并减少维生素D缺乏的老年人的福尔斯。然而，很少有人知道的潜在机制或作用1，25-D3在促进肌细胞分化在细胞和/或分子水平。在这项研究中，我们研究了1，25-D3对成肌细胞增殖，进展和分化成肌管的影响。C2 C12成肌细胞用1，25-D3或安慰剂处理1、3、4、7和10 d。通过定量RT-PCR、Western印迹和免疫荧光分析维生素D受体表达。通过免疫细胞化学、PCR阵列、定量RT-PCR和Western印迹评估肌肉谱系、促生和抗生肌以及增殖标记物的表达。向C2 C12成肌细胞中添加1，25-D3 1）增加维生素D受体的表达和核转位，2）降低细胞增殖，3）降低IGF-I表达，和4）通过增加IGF-II和卵泡抑素表达和降低肌生成抑制素（唯一已知的肌肉质量负调节剂）的表达来促进肌生成分化，而不改变生长分化因子11的表达。这项研究确定了肌肉调节的关键维生素D相关分子途径，并支持在选定的肌肉疾病条件下进行维生素D干预研究的基本原理。（内分泌学152：2976-2986，2011）
Skeletal muscle wasting is an important public health problem associated with aging, chronic disease, cancer, kidney dialysis, and HIV/AIDS. 1,25-Dihydroxyvitamin D (1,25-D3), the active form of vitamin D, is widely recognized for its regulation of calcium and phosphate homeostasis in relation to bone development and maintenance and for its calcemic effects on target organs, such as intestine, kidney, and parathyroid glands. Emerging evidence has shown that vitamin D administration improves muscle performance and reduces falls in vitamin D-deficient older adults. However, little is known of the underlying mechanism or the role 1,25-D3 plays in promoting myogenic differentiation at the cellular and/or molecular level. In this study, we examined the effect of 1,25-D3 on myoblast cell proliferation, progression, and differentiation into myotubes. C2C12 myoblasts were treated with 1,25-D3 or placebo for 1, 3, 4, 7, and 10 d. Vitamin D receptor expression was analyzed by quantitative RT-PCR, Western blottings and immunofluorescence. Expression of muscle lineage, pro- and antimyogenic, and proliferation markers was assessed by immunocytochemistry, PCR arrays, quantitative RT-PCR, and Western blottings. Addition of 1,25-D3 to C2C12 myoblasts 1) increased expression and nuclear translocation of the vitamin D receptor, 2) decreased cell proliferation, 3) decreased IGF-I expression, and 4) promoted myogenic differentiation by increasing IGF-II and follistatin expression and decreasing the expression of myostatin, the only known negative regulator of muscle mass, without changing growth differentiation factor 11 expression. This study identifies key vitamin D-related molecular pathways for muscle regulation and supports the rationale for vitamin D intervention studies in select muscle disorder conditions. (Endocrinology 152: 2976-2986, 2011)