Ibandronate concomitantly blocks immobilization-induced bone and muscle atrophy.
Ibandronate concomitantly blocks immobilization-induced bone and muscle atrophy.
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伊班膦酸盐同时阻止固定引起的骨和肌肉萎缩。
DOI：
10.1016/j.bbrc.2016.10.112
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Miyamoto T.
中科院分区：
文献类型：
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作者：
Watanabe R;Fujita N;Takeda S;Sato Y;Kobayashi T;Morita M;Oike T;Miyamoto K;Matsumoto Y;Matsumoto M;Nakamura M;Miyamoto T.
在固定条件下，骨骼和肌肉的体积都会随之减少；然而，目前还没有一种药物可以同时阻断这些结果。双膦酸盐在临床上被用来抑制破骨细胞依赖的骨吸收，但它们对肌肉的影响在很大程度上是未知的。在此，我们表明，骨骼肌是双膦酸伊班磷酸酯(IBN)的直接靶点，在小鼠肌肉萎缩模型中，IBN的应用显著抑制了肌肉体积的减少和Atrogin-1和MuRF1的诱导，这两种萎缩基因都是萎缩的基因。IBN治疗还显著阻断了体内固定化诱导的骨丢失。我们还报道了体外培养的肌源性C2C12细胞在血清饥饿后，阿托品上游的Atrogin-1和MuRF1蛋白的表达和Smad2/3蛋白的积累，IBN处理显著抑制了这种作用。有趣的是，IBN对C2C12细胞的作用被泛素/蛋白酶体抑制剂MG132消除，这表明IBN是通过泛素-蛋白酶体系统发挥作用的。我们的发现为IBN在预防肌肉萎缩中的作用提供了新的见解。
Both bone and muscle volume is concomitantly reduced under immobilization conditions; however, no single drug is currently available to block these outcomes simultaneously. Bisphosphonates are utilized clinically to inhibit osteoclast-dependent bone resorption, but their effects on muscle are largely unknown. Here we show that skeletal muscle is a direct target of the bisphosphonate ibandronate (IBN) and that reduced muscle volume and induction ofAtrogin-1andMuRF1, both atrogenes, are significantly inhibited by IBN administrationin vivousing a mouse model of muscle atrophy. IBN treatment also significantly blocked immobilization-induced bone lossin vivo. We also report that expression ofAtrogin-1andMuRF1and accumulation of Smad2/3 proteins, which are upstream of atrogines, occurred following serum starvation of myogenic C2C12 cellsin vitro, effects significantly inhibited by IBN treatment. Interestingly, IBN effects on C2C12 cells were abrogated by MG132, an ubiquitin/proteasome inhibitor, suggesting that IBN functions via the ubiquitin-proteasome system. Our findings lend new insight into the role of IBN in preventing muscle atrophy.