1. The regulation of iron metabolism by hepcidin contributes to unloading-induced bone loss
- Author
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Shukuan Ling, Yuheng Li, Weijia Sun, Hailin Song, Jinqiao Li, Guohui Zhong, Yingxian Li, Zi Xu, Linhao You, Guangjun Nie, Dingsheng Zhao, Yan-Zhong Chang, Chenyang Zhao, and Jinping Song
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Histology ,Iron Overload ,Physiology ,Endocrinology, Diabetes and Metabolism ,Iron ,Down-Regulation ,Transferrin receptor ,Deferoxamine ,Iron Chelating Agents ,Bone resorption ,Bone and Bones ,03 medical and health sciences ,Hepcidins ,Osteoclast ,Hepcidin ,Internal medicine ,medicine ,Animals ,Gene Silencing ,Bone Resorption ,RNA, Small Interfering ,Deferoxamine mesylate ,biology ,Chemistry ,Osteoblast ,Iron response element ,Absorption, Physiological ,Up-Regulation ,Mice, Inbred C57BL ,Bone morphogenetic protein 6 ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Hindlimb Suspension ,Liver ,biology.protein - Abstract
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.
- Published
- 2016