海西定
下调和上调
成骨细胞
化学
内分泌学
去铁胺
破骨细胞
DMT1型
转铁蛋白受体
内科学
铁转运蛋白
骨重建
运输机
转铁蛋白
受体
贫血
医学
生物化学
体外
基因
作者
Zi Xu,Weijia Sun,Yuheng Li,Shukuan Ling,Chenyang Zhao,Guangming Zhong,Di Zhao,Jinping Song,Hailin Song,Jinqiao Li,Linhao You,Guangjun Nie,Yan‐Zhong Chang,Yingxian Li
出处
期刊:Bone
[Elsevier]
日期:2017-01-01
卷期号:94: 152-161
被引量:56
标识
DOI:10.1016/j.bone.2016.09.023
摘要
Iron overload inhibits osteoblast function and promotes osteoclastogenesis. Hepcidin plays an important role in this process. The changes in iron content and the regulation of hepcidin under unloading-induced bone loss remain unknown. A hindlimb suspension model was adopted to simulate unloading-induced bone loss in mice. The results showed that iron deposition in both liver and bone was markedly increased in hindlimb unloaded mice, and was accompanied by the upregulation of osteoclast activity and downregulation of osteoblast activity. The iron chelator deferoxamine mesylate (DFO) reduced the iron content in bone and alleviated unloading-induced bone loss. The increased iron content in bone was mainly a result of the upregulation of transferrin receptor 1 (TfR1) and divalent metal transporter 1 with iron response element (DMT1 + IRE), rather than changes in the iron transporter ferroportin 1 (FPN1). The hepcidin level in the liver was significantly higher, while the FPN1 level in the duodenum was substantially reduced. However, there were no changes in the FPN1 level in bone tissue. During hindlimb unloading, downregulation of hepcidin by siRNA increased iron uptake in bone and liver, which aggravated unloading-induced bone loss. In summary, these data show that unloading-induced bone loss was orchestrated by iron overload and coupled with the regulation of hepcidin by the liver.
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