Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis

Simão, M.; Camacho, A.; Ostertag, A.; Cohen-Solal, M.; Pinto, I.; Porto, G.; Hang Korng, E.; Cancela, M.

Publication

Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis

2018-11-14Journal article

dc.contributor.author	Simão, M.
dc.contributor.author	Camacho, A.
dc.contributor.author	Ostertag, A.
dc.contributor.author	Cohen-Solal, M.
dc.contributor.author	Pinto, I.
dc.contributor.author	Porto, G.
dc.contributor.author	Hang Korng, E.
dc.contributor.author	Cancela, M.
dc.date.accessioned	2020-02-18T12:19:32Z
dc.date.available	2020-02-18T12:19:32Z
dc.date.issued	2018-11-14
dc.description.abstract	Osteoporosis is associated with chronic iron overload secondary to hereditary hemochromatosis (HH), but the causative mechanisms are incompletely understood. The main objective of this study was to investigate the role of dietary iron on osteoporosis, using as biological model the Hfe-KO mice, which have a systemic iron overload. We showed that these mice show an increased susceptibility for developing a bone loss phenotype compared to WT mice, which can be exacerbated by an iron rich diet. The dietary iron overload caused an increase in inflammation and iron incorporation within the trabecular bone in both WT and Hfe-KO mice. However, the osteoporotic phenotype was only evident in Hfe-KO mice fed the iron-enriched diet. This appeared to result from an imbalance between bone formation and bone resorption driven by iron toxicity associated to Hfe-KO and confirmed by a decrease in bone microarchitecture parameters (identified by micro-CT) and osteoblast number. These findings were supported by the observed downregulation of bone metabolism markers and upregulation of ferritin heavy polypeptide 1 (Fth1) and transferrin receptor-1 (Tfrc), which are associated with iron toxicity and bone loss phenotype. In WT mice the iron rich diet was not enough to promote a bone loss phenotype, essentially due to the concomitant depression of bone resorption observed in those animals. In conclusion the dietary challenge influences the development of osteoporosis in the HH mice model thus suggesting that the iron content in the diet may influence the osteoporotic phenotype in systemic iron overload conditions.	pt_PT
dc.description.sponsorship	his research was partially supported by National Funds through Foundation for Science and Technology (FCT), under the project “CCMAR/Multi/04326/2013” and Norte-01-0145-FEDER-000012 –“Structured program on bioengineered therapies for infectious diseases and tissue regeneration”. M. Simão was supported by a PhD fellowship from the Portuguese Foundation for Science and Technology (FCT) with the reference SFRH/BD/77056/2011. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.	pt_PT
dc.description.version	info:eu-repo/semantics/publishedVersion	pt_PT
dc.identifier.citation	Simão M, Camacho A, Ostertag A, et al. Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis [published correction appears in PLoS One. 2019 Apr 29;14(4):e0216377]. PLoS One. 2018;13(11):e0207441. Published 2018 Nov 14.	pt_PT
dc.identifier.doi	10.1371/journal.pone.0207441	pt_PT
dc.identifier.issn	1932-6203
dc.identifier.uri	http://hdl.handle.net/10400.16/2314
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Public Library of Science	pt_PT
dc.relation.publisherversion	https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207441	pt_PT
dc.title	Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.citation.conferencePlace	United States of America	pt_PT
oaire.citation.issue	11	pt_PT
oaire.citation.startPage	e0207441	pt_PT
oaire.citation.title	PloS one	pt_PT
oaire.citation.volume	13	pt_PT
person.familyName	Porto
person.givenName	Graça
person.identifier.ciencia-id	431B-A46D-D7A0
person.identifier.orcid	0000-0002-1923-4638
person.identifier.rid	J-7939-2013
person.identifier.scopus-author-id	55910746800
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT
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