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PLoS One. 2016 Feb 1;11(2):e0148292. doi: 10.1371/journal.pone.0148292. eCollection 2016.

Decreased Bone Formation Explains Osteoporosis in a Genetic Mouse Model of Hemochromatosiss.

Author information

1
INSERM UMR U991, F- 35033, Rennes, France.
2
Université de Rennes 1, IFR 140, F- 35043, Rennes, France.
3
GEROM Groupe Etude Remodelage Osseux et bioMatériaux LHEA, IRIS-IBM, Institut de biologie en santé, CHU, F- 49933, Angers, France.
4
INSERM U1043, F- 31300, Toulouse, France.
5
Service des Maladies du Foie, Hôpital Pontchaillou, CHU, F- 35033, Rennes, France.
6
Service de Rhumatologie, Hôpital Sud, CHU, F- 35033, Rennes, France.

Abstract

Osteoporosis may complicate iron overload diseases such as genetic hemochromatosis. However, molecular mechanisms involved in the iron-related osteoporosis remains poorly understood. Recent in vitro studies support a role of osteoblast impairment in iron-related osteoporosis. Our aim was to analyse the impact of excess iron in Hfe-/- mice on osteoblast activity and on bone microarchitecture. We studied the bone formation rate, a dynamic parameter reflecting osteoblast activity, and the bone phenotype of Hfe-/- male mice, a mouse model of human hemochromatosis, by using histomorphometry. Hfe-/- animals were sacrificed at 6 months and compared to controls. We found that bone contains excess iron associated with increased hepatic iron concentration in Hfe-/- mice. We have shown that animals with iron overload have decreased bone formation rate, suggesting a direct impact of iron excess on active osteoblasts number. For bone mass parameters, we showed that iron deposition was associated with bone loss by producing microarchitectural impairment with a decreased tendency in bone trabecular volume and trabecular number. A disorganization of trabecular network was found with marrow spaces increased, which was confirmed by enhanced trabecular separation and star volume of marrow spaces. These microarchitectural changes led to a loss of connectivity and complexity in the trabecular network, which was confirmed by decreased interconnectivity index and increased Minkowski's fractal dimension. Our results suggest for the first time in a genetic hemochromatosis mouse model, that iron overload decreases bone formation and leads to alterations in bone mass and microarchitecture. These observations support a negative effect of iron on osteoblast recruitment and/or function, which may contribute to iron-related osteoporosis.

PMID:
26829642
PMCID:
PMC4734777
DOI:
10.1371/journal.pone.0148292
[Indexed for MEDLINE]
Free PMC Article

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