Hepcidin deficiency undermines bone load-bearing capacity through inducing iron overload.
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.
['Sun|Li|L|', 'Guo|Wenli|W|', 'Yin|Chunyang|C|', 'Zhang|Shuping|S|', 'Qu|Guangbo|G|', 'Hou|Yanli|Y|', 'Rong|Haiqin|H|', 'Ji|Hong|H|', 'Liu|Sijin|S|']
D000818:Animals D001862:Bone Resorption D001842:Bone and Bones D064451:Hepcidins D006706:Homeostasis D007501:Iron D019190:Iron Overload D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D010012:Osteogenesis D016474:Weight-Bearing
Hepcidin deficiency Iron overload Bone resorption Bone strength