Hepcidin protects against iron overload-induced inhibition of bone formation in zebrafish
Iron overload increases the risk of osteoporosis, which leads to an increase in the incidences of bone fracture after menopause. In vitro studies have demonstrated that excess iron can inhibit osteoblast activity. Hepcidin, a central regulator of iron homeostasis, prevents iron overload, and thus, it is considered to have anti-osteoporosis effects. In this study, a zebrafish model was employed to investigate the therapeutic role of hepcidin in iron overload-induced inhibition of bone formation. Our results show that ferric ammonium citrate (FAC) treatment decreased osteoblast-specific gene expression (runx2a, runx2b, and bglap) and bone mineralization in the zebrafish embryo, accompanied with increased whole-body iron levels and oxidative stress. Bone mineralization and osteoblast-specific gene expression increased with the microinjection of hepcidin-flag Capped-mRNA into zebrafish embryos. Moreover, the whole-body iron content and oxidative stress in the iron-overloaded zebrafish embryos decreased when microinjection of hepcidin preceded the FAC treatment. Therefore, our study suggests that hepcidin could prevent and rescue reduced bone formation caused by FAC treatment by preventing iron absorption.
KeywordsHepcidin Iron overload Bone formation Zebrafish Osteoblast Oxidative stress
inductively coupled plasma mass spectrometry
ferric ammonium citrate
This work was supported in part by grants from the National Natural Science Foundation of China (81602864), National Advance Natural Science Foundation of China (SDFEGJ1601), Jiangsu Province Special Medical Grant (BL2014044), Suzhou Clinical Key Special Diseases Fund (LCZX210305), and Jiangsu Youth Medical Foundation of China (QNRC2016149).
Compliance with ethical standards
Animal care and all the experiments were performed in accordance with the institutional ethical guidelines for animal experiments, and all experimental procedures using fish were approved by the Soochow University Committee on Animal Use and Care.
Conflict of interest
The authors declare that they have no conflict of interest.
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