title: Hepcidin deficiency undermines bone load-bearing capacity through inducing iron overload.
abstract: Osteoporosis is one of the leading disorders among aged people. Bone loss results from a number of physiological alterations, such as estrogen decline and aging. Meanwhile, iron overload has been recognized as a risk factor for bone loss. Systemic iron homeostasis is fundamentally governed by the hepcidin-ferroportin regulatory axis, where hepcidin is the key regulator. Hepcidin deficiency could induce a few disorders, of which iron overload is the most representative phenotype. However, there was little investigation of the effects of hepcidin deficiency on bone metabolism. To this end, hepcidin-deficient (Hamp1(-/-)) mice were employed to address this issue. Our results revealed that significant iron overload was induced in Hamp1(-/-) mice. Importantly, significant decreases of maximal loading and maximal bending stress were found in Hamp1(-/-) mice relative to wildtype (WT) mice. Moreover, the levels of the C-telopeptide of type I collagen (CTX-1) increased in Hamp1(-/-) mice. Therefore, hepcidin deficiency resulted in a marked reduction of bone load-bearing capacity likely through enhancing bone resorption, suggesting a direct correlation between hepcidin deficiency and bone loss. Targeting hepcidin or the pathway it modulates may thus represent a therapeutic for osteopenia or osteoporosis.
authors.affiliation: School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan 250062, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Qu
authors.affiliation: Shandong Institute of Endocrine and Metabolic Diseases, Shandong Academy of Medical Sciences, Jinan 250062, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Shandong Institute of Endocrine and Metabolic Diseases, Shandong Academy of Medical Sciences, Jinan 250062, China.
authors.forename: Haiqin
authors.initials: H
authors.lastname: Rong
authors.affiliation: Shandong Institute of Endocrine and Metabolic Diseases, Shandong Academy of Medical Sciences, Jinan 250062, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address: sjliu@rcees.ac.cn.
authors.forename: Sijin
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000235:genetics* / Q000503:physiopathology; D001842:Bone and Bones / Q000502:physiology*; D064451:Hepcidins / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010012:Osteogenesis / Q000235:genetics; D016474:Weight-Bearing
chemical_list: C579599:Hamp protein, mouse; D064451:Hepcidins; D007501:Iron
keywords: Bone resorption; Bone strength; Hepcidin deficiency; Iron overload