Rapamycin improves bone mass in high-turnover osteoporosis with iron accumulation through positive effects on osteogenesis and angiogenesis
Rapamycin improves bone mass in high-turnover osteoporosis with iron accumulation through positive effects on osteogenesis and angiogenesis
复制标题
雷帕霉素通过对成骨和血管生成的积极作用，通过铁积累来改善高周转骨质疏松症的骨量
DOI：
10.1016/j.bone.2018.12.019
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发表时间：
2019
期刊：
影响因子：
4.1
通讯作者：
Xu Youjia
中科院分区：
文献类型：
--
作者：
Wu Jiadong;Wang Aifei;Wang Xiao;Li Guangfei;Jia Peng;Shen Guangsi;Chen Bin;Yuan Ye;Zhang Hui;Yang Fan;Xu Youjia
铁蓄积是I型骨质疏松症的一个独立危险因素，但其分子机制尚不明确，有效的治疗方法也未见报道。在这里，我们发现mTOR的水平在具有铁积累的野生型小鼠模型和具有铁积累的高转换骨质疏松症的转基因小鼠模型（Hepc−/−）中均增加。我们表明，在骨骼和体外，mTOR水平的增加可以通过Cxcl 9抑制骨生成和血管生成。在小鼠模型中通过雷帕霉素和体外通过siRNA转染抑制mTOR恢复了骨生成和血管生成。这些发现揭示了mTOR在具有铁积累的高转换骨质疏松症中的骨生成和血管生成中的作用，并表明雷帕霉素靶向mTOR改善骨生成和血管生成以改善骨量。
Iron accumulation is an independent risk factor for type I osteoporosis, but the molecular mechanisms of the phenomenon are not well defined, and effective therapy has not been reported. Here, we found that the level of mTOR was increased both in wild-type mouse models with iron accumulation and transgenic mouse models (Hepc−/−) of high-turnover osteoporosis with iron accumulation. We show that an increased level of mTOR can depress osteogenesis and angiogenesis by Cxcl9 both in bone and in vitro. Suppression of mTOR in mouse models by rapamycin and in vitro by siRNA transfection recovered both osteogenesis and angiogenesis. These findings revealed the role of mTOR in osteogenesis and angiogenesis in high-turnover osteoporosis with iron accumulation and showed that rapamycin targeting of mTOR ameliorates osteogenesis and angiogenesis to improve bone mass.