Disruption of the hepcidin/ferroportin regulatory circuitry causes low axial bone mass in mice

Ferroportin (FPN) is the only known iron exporter. Mutations conferring resistance of FPN to hepcidin-mediated degradation cause the iron overload disorder hereditary hemochromatosis type 4. While iron overload is associated with low bone mass, the mechanisms involved are not completely understood....

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Published in:Bone (New York, N.Y.) N.Y.), 2020-08, Vol.137, p.115400-115400, Article 115400
Main Authors: Ledesma-Colunga, Maria G., Baschant, Ulrike, Fiedler, Imke A.K., Busse, Björn, Hofbauer, Lorenz C., Muckenthaler, Martina U., Altamura, Sandro, Rauner, Martina
Format: Article
Language:English
Subjects:
Bone homeostasis
Ferroportin
Iron
Osteoblast
Osteoclast
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Summary:Ferroportin (FPN) is the only known iron exporter. Mutations conferring resistance of FPN to hepcidin-mediated degradation cause the iron overload disorder hereditary hemochromatosis type 4. While iron overload is associated with low bone mass, the mechanisms involved are not completely understood. Here, we aimed to investigate whether the disruption in the hepcidin/FPN axis in FpnC326S mice and subsequent systemic iron accumulation impacts on bone tissue to a similar extent as in Hfe−/− mice, which are hallmarked by a milder iron overload phenotype. Hfe−/− and FpnC326S mice show increased plasma iron levels and liver iron content, whereas iron overload was more pronounced in FpnC326S compared to Hfe−/− mice. Bone volume fraction and trabecular thickness at the femur were not different between 10 and 14-week-old male wild-type (WT), Hfe−/− and FpnC326S mice. By contrast, both Hfe−/− and FpnC326S mice exhibited a lower bone volume fraction [Hfe−/−, 24%; FpnC326S, 33%; p 
ISSN:8756-3282
1873-2763
DOI:10.1016/j.bone.2020.115400