Disruption of the hepcidin/ferroportin regulatory circuitry causes low axial bone mass in mice
Standard
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.
in: BONE, Jahrgang 137, 08.2020, S. 115400.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Disruption of the hepcidin/ferroportin regulatory circuitry causes low axial bone mass in mice
AU - Ledesma-Colunga, Maria G
AU - Baschant, Ulrike
AU - Fiedler, Imke A K
AU - Busse, Björn
AU - Hofbauer, Lorenz C
AU - Muckenthaler, Martina U
AU - Altamura, Sandro
AU - Rauner, Martina
N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
U2 - 10.1016/j.bone.2020.115400
DO - 10.1016/j.bone.2020.115400
M3 - SCORING: Journal article
C2 - 32380257
VL - 137
SP - 115400
JO - BONE
JF - BONE
SN - 8756-3282
ER -