PMID- 26829642
OWN - NLM
STAT- MEDLINE
DCOM- 20160712
LR  - 20161126
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 2
DP  - 2016
TI  - Decreased Bone Formation Explains Osteoporosis in a Genetic Mouse Model of
      Hemochromatosiss.
PG  - e0148292
LID - 10.1371/journal.pone.0148292 [doi]
AB  - 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.
FAU - Doyard, Mathilde
AU  - Doyard M
AD  - INSERM UMR U991, F- 35033, Rennes, France.
AD  - Universite de Rennes 1, IFR 140, F- 35043, Rennes, France.
FAU - Chappard, Daniel
AU  - Chappard D
AD  - GEROM Groupe Etude Remodelage Osseux et bioMateriaux LHEA, IRIS-IBM, Institut de 
      biologie en sante, CHU, F- 49933, Angers, France.
FAU - Leroyer, Patricia
AU  - Leroyer P
AD  - INSERM UMR U991, F- 35033, Rennes, France.
AD  - Universite de Rennes 1, IFR 140, F- 35043, Rennes, France.
FAU - Roth, Marie-Paule
AU  - Roth MP
AD  - INSERM U1043, F- 31300, Toulouse, France.
FAU - Loreal, Olivier
AU  - Loreal O
AD  - INSERM UMR U991, F- 35033, Rennes, France.
AD  - Universite de Rennes 1, IFR 140, F- 35043, Rennes, France.
AD  - Service des Maladies du Foie, Hopital Pontchaillou, CHU, F- 35033, Rennes,
      France.
FAU - Guggenbuhl, Pascal
AU  - Guggenbuhl P
AD  - INSERM UMR U991, F- 35033, Rennes, France.
AD  - Universite de Rennes 1, IFR 140, F- 35043, Rennes, France.
AD  - Service de Rhumatologie, Hopital Sud, CHU, F- 35033, Rennes, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160201
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Hemochromatosis Protein)
RN  - 0 (Hfe protein, mouse)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Proteins)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Animals
MH  - Bone and Bones/*metabolism/*pathology
MH  - Calcification, Physiologic
MH  - Disease Models, Animal
MH  - Hemochromatosis/*complications/*genetics/metabolism
MH  - Hemochromatosis Protein
MH  - Histocompatibility Antigens Class I/genetics
MH  - Iron/metabolism
MH  - Liver/metabolism/pathology
MH  - Male
MH  - Membrane Proteins/deficiency/genetics
MH  - Mice
MH  - Mice, Knockout
MH  - *Osteogenesis
MH  - Osteoporosis/*etiology/*pathology
PMC - PMC4734777
EDAT- 2016/02/02 06:00
MHDA- 2016/07/13 06:00
CRDT- 2016/02/02 06:00
PHST- 2015/10/07 00:00 [received]
PHST- 2016/01/15 00:00 [accepted]
PHST- 2016/02/02 06:00 [entrez]
PHST- 2016/02/02 06:00 [pubmed]
PHST- 2016/07/13 06:00 [medline]
AID - 10.1371/journal.pone.0148292 [doi]
AID - PONE-D-15-40763 [pii]
PST - epublish
SO  - PLoS One. 2016 Feb 1;11(2):e0148292. doi: 10.1371/journal.pone.0148292.
      eCollection 2016.