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Disruption of the hepcidin/ferroportin regulatory circuitry causes low axial bone mass in mice.
Ledesma-Colunga, Maria G; Baschant, Ulrike; Fiedler, Imke A K; Busse, Björn; Hofbauer, Lorenz C; Muckenthaler, Martina U; Altamura, Sandro; Rauner, Martina.
Afiliação
  • Ledesma-Colunga MG; Department of Medicine III, Technische Universität Dresden, Dresden, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany.
  • Baschant U; Department of Medicine III, Technische Universität Dresden, Dresden, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany.
  • Fiedler IAK; Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Busse B; Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Hofbauer LC; Department of Medicine III, Technische Universität Dresden, Dresden, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany.
  • Muckenthaler MU; Department of Pediatric Hematology, Oncology and Immunology, University of Heidelberg, Heidelberg, Germany.
  • Altamura S; Department of Pediatric Hematology, Oncology and Immunology, University of Heidelberg, Heidelberg, Germany.
  • Rauner M; Department of Medicine III, Technische Universität Dresden, Dresden, Germany; Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany. Electronic address: martina.rauner@ukdd.de.
Bone ; 137: 115400, 2020 08.
Article em En | MEDLINE | ID: mdl-32380257
ABSTRACT
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 < 0.05] and trabecular thickness [Hfe-/-, 10%; FpnC326S, 15%; p < 0.05] in the fourth lumbar vertebra compared to WT mice. Analysis of the bone formation rate at the tibia showed no difference in both genotypes, but it was reduced in the vertebral bone of FpnC326S [36%, p < 0.05] compared to WT mice. Serum levels of the bone formation marker, P1NP, were significantly reduced in both, Hfe-/- and FpnC326S compared with WT mice [Hfe-/-, 35%; FpnC326S, 40%; p < 0.05]. Also, the intrinsic differentiation capacity of FpnC326S osteoblasts was impaired. Osteoclast parameters were not grossly affected. Interestingly, the liver iron content and plasma iron levels negatively correlated with the bone formation rate and serum levels of P1NP. Thus, disruption of the hepcidin/ferroportin regulatory axis in FpnC326S mice results in axial bone loss due to suppressed bone formation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sobrecarga de Ferro / Proteínas de Transporte de Cátions / Hemocromatose Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sobrecarga de Ferro / Proteínas de Transporte de Cátions / Hemocromatose Idioma: En Ano de publicação: 2020 Tipo de documento: Article