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Iron overload in a murine model of hereditary hemochromatosis is associated with accelerated progression of osteoarthritis under mechanical stress

2016-07Journal article Restricted access
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dc.contributor.authorCamacho, A.
dc.contributor.authorF. Simao, Marcio
dc.contributor.authorEa, H. -K.
dc.contributor.authorCohen-Solal, M.
dc.contributor.authorRichette, P.
dc.contributor.authorBranco, J.
dc.contributor.authorCancela, Leonor
dc.date.accessioned2017-04-07T15:57:05Z
dc.date.available2017-04-07T15:57:05Z
dc.date.issued2016-07
dc.description.abstractObjective: Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress.Design: OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery.Results: Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery.Conclusions: HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA.
dc.identifier.doihttps://doi.org/10.1016/j.joca.2015.09.007
dc.identifier.issn1063-4584
dc.identifier.otherAUT: LCA007;
dc.identifier.urihttp://hdl.handle.net/10400.1/9606
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relationIDENTIFICATION OF THE MOLECULAR PLAYERS INVOLVED IN HEREDITARY HEMOCHROMATOSIS-RELATED OSTEOARTHRITIS
dc.relation.isbasedonWOS:000370258600014
dc.subjectIron overload
dc.subjectMouse model
dc.subjectHereditary hemochromatosis
dc.subjectOsteoarthritis
dc.subjectMechanical stress
dc.titleIron overload in a murine model of hereditary hemochromatosis is associated with accelerated progression of osteoarthritis under mechanical stress
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleIDENTIFICATION OF THE MOLECULAR PLAYERS INVOLVED IN HEREDITARY HEMOCHROMATOSIS-RELATED OSTEOARTHRITIS
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04326%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F77056%2F2011/PT
oaire.citation.endPage502
oaire.citation.issue3
oaire.citation.startPage494
oaire.citation.titleOsteoarthritis and Cartilage
oaire.citation.volume24
oaire.fundingStream5876
oaire.fundingStreamOE
person.familyNameSimĂŁo
person.familyNameCancela
person.givenNameMĂĄrcio
person.givenNameM. Leonor
person.identifier.ciencia-idF819-2D45-A17F
person.identifier.orcid0000-0001-9658-0895
person.identifier.orcid0000-0003-3114-6662
person.identifier.scopus-author-id35739158900
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a CiĂȘncia e a Tecnologia
project.funder.nameFundação para a CiĂȘncia e a Tecnologia
rcaap.rightsrestrictedAccess
rcaap.typearticle
relation.isAuthorOfPublication72f41d8a-d842-4519-8800-d4097fbee9ad
relation.isAuthorOfPublicationb9bbfe32-3dfe-4131-ad14-a4394008447f
relation.isAuthorOfPublication.latestForDiscovery72f41d8a-d842-4519-8800-d4097fbee9ad
relation.isProjectOfPublication868b4818-3efa-4edb-9202-c464d64fd38f
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relation.isProjectOfPublication.latestForDiscovery868b4818-3efa-4edb-9202-c464d64fd38f

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