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Despite Genetic Iron Overload, Hfe-Hemochromatosis Mice Do Not Show Bone Loss
Alessa Wagner1, Betül Alan1, Dilay Yilmaz1
1Institute of Comparative Molecular Endocrinology, University of Ulm Ulm Germany.
Insights
Genetic iron overload from HFE gene mutations does not harm bone integrity in mice. Studies show HFE protein is not essential for maintaining bone health or iron balance.
Area of Science:
- Biochemistry
- Genetics
- Bone Biology
Background:
- Mutations in the HFE gene cause hereditary hemochromatosis, a common iron overload disorder in Caucasians.
- Iron accumulation in HFE patients and Hfe-deficient mice leads to various pathologies, including concerns about bone health.
- Previous research suggested a link between iron overload and osteoporosis in HFE hemochromatosis.
Purpose of the Study:
- To investigate the relationship between systemic iron overload and bone microarchitecture in Hfe-deficient mice.
- To determine the role of Hfe in osteoblasts and osteoclasts for bone and iron homeostasis.
Main Methods:
- Utilized Hfe-deficient (Hfe-/-) mice to model genetic iron overload.
- Assessed long bone microarchitecture using micro-computed tomography.
- Evaluated the function of Hfe in osteoblasts and osteoclasts.
Main Results:
- Systemic iron overload in Hfe-/- mice did not result in impaired long bone microarchitecture.
- Hfe function in osteoblasts and osteoclasts was found to be dispensable for maintaining bone integrity and iron homeostasis.
- Hfe-/- mice exhibited normal physiological bone homeostasis despite systemic iron overload.
Conclusions:
- Systemic iron overload, as observed in Hfe-/- mice, does not negatively impact bone integrity.
- Hfe is not essential for maintaining bone and iron homeostasis under steady-state conditions.
- The study challenges the concept of iron overload-induced osteoporosis in HFE hemochromatosis.
Abstract:
One of the most prevalent genetic iron overload disorders in Caucasians is caused by mutations in the HFE gene. Both HFE patients and Hfe-mouse models develop a progressive accumulation of iron in the parenchymal cells of various tissues, eventually resulting in liver cirrhosis, hepatocellular carcinoma, cardiomyopathies, hypogonadism, and other pathologies. Clinical data and preclinical models have brought considerable attention to the correlation between iron overload and the development of osteoporosis in HFE/Hfe hemochromatosis. Our study critically challenges this concept. We show that systemic iron overload, at the degree present in Hfe -/- mice, does not associate with the microarchitecture impairment of long bones, thus excluding a negative effect of iron overload on bone integrity. We further reveal that Hfe actions in osteoblasts and osteoclasts are dispensable for the maintenance of bone and iron homeostasis in mice under steady-state conditions. We conclude that, despite systemic iron overload, Hfe -/- mice present normal physiological bone homeostasis. © 2019 The Authors. JBMR Plus in published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
