Repository logo
 
Publication

Intracellular iron uptake is favored in Hfe-KO mouse primary chondrocytes mimicking an osteoarthritis-related phenotype

2019-07Journal article Open access
Simple item page
dc.contributor.authorF. Simao, Marcio
dc.contributor.authorJ. Gavaia, Paulo
dc.contributor.authorCamacho, Antonio
dc.contributor.authorPorto, Graca
dc.contributor.authorJorge Pinto, I.
dc.contributor.authorEa, Hang-Korng
dc.contributor.authorCancela, M. Leonor
dc.date.accessioned2020-07-24T10:52:00Z
dc.date.available2020-07-24T10:52:00Z
dc.date.issued2019-07
dc.description.abstractHFE-hemochromatosis is a disease characterized by a systemic iron overload phenotype mainly associated with mutations in the HFE protein (HFE) gene. Osteoarthritis (OA) has been reported as one of the most prevalent complications in HFE-hemochromatosis patients, but the mechanisms associated with its onset and progression remain incompletely understood. In this study, we have characterized the response to high iron concentrations of a primary culture of articular chondrocytes isolated from newborn Hfe-KO mice and compared the results with that of a similar experiment developed in cells from C57BL/6 wild-type (wt) mice. Our data provide evidence that both wt- and Hfe-KO-derived chondrocytes, when exposed to 50 mu M iron, develop characteristics of an OA-related phenotype, such as an increased expression of metalloproteases, a decreased extracellular matrix production, and a lower expression level of aggrecan. In addition, Hfe-KO cells also showed an increased expression of iron metabolism markers and MMP3, indicating an increased susceptibility to intracellular iron accumulation and higher levels of chondrocyte catabolism. Accordingly, upon treatment with 50 mu M iron, these chondrocytes were found to preferentially differentiate toward hypertrophy with increased expression of collagen I and transferrin and downregulation of SRY (sex-determining region Y)-box containing gene 9 (Sox9). In conclusion, high iron exposure can compromise chondrocyte metabolism, which, when simultaneously affected by an Hfe loss of function, appears to be more susceptible to the establishment of an OA-related phenotype.
dc.description.sponsorshipEuropean Regional Development FundEuropean Union (EU) [EMBRC.PT Alg-01-0145-FEDER-022121, Norte-01-0145-FEDER-000012]
dc.description.sponsorshipFundacao para a Ciencia e a TecnologiaPortuguese Foundation for Science and Technology [SFRH/BD/77056/2011]
dc.description.sponsorshipPortuguese Foundation for Science and TechnologyPortuguese Foundation for Science and Technology
dc.description.sponsorshipPortuguese Science and Technology FoundationPortuguese Foundation for Science and Technology
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1002/biof.1520
dc.identifier.issn0951-6433
dc.identifier.issn1872-8081
dc.identifier.urihttp://hdl.handle.net/10400.1/14300
dc.language.isoeng
dc.peerreviewedyes
dc.publisherWiley
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectInduced joint damage
dc.subjectHereditary hemochromatosis
dc.subjectTransferrin receptor
dc.subjectGenetic hemochromatosis
dc.subjectCartilage degeneration
dc.subjectArticular-cartilage
dc.subjectMurine model
dc.subjectArthropathy
dc.subjectBone
dc.subjectMetabolism
dc.titleIntracellular iron uptake is favored in Hfe-KO mouse primary chondrocytes mimicking an osteoarthritis-related phenotype
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage597
oaire.citation.issue4
oaire.citation.startPage583
oaire.citation.titleBioFactors
oaire.citation.volume45
person.familyNameSimão
person.familyNameGavaia
person.familyNameCancela
person.givenNameMárcio
person.givenNamePaulo
person.givenNameM. Leonor
person.identifier.ciencia-idF819-2D45-A17F
person.identifier.ciencia-idB619-FC16-D007
person.identifier.orcid0000-0001-9658-0895
person.identifier.orcid0000-0002-9582-1957
person.identifier.orcid0000-0003-3114-6662
person.identifier.ridA-6470-2011
person.identifier.scopus-author-id35739158900
person.identifier.scopus-author-id6507104377
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication72f41d8a-d842-4519-8800-d4097fbee9ad
relation.isAuthorOfPublication9dca2139-21a4-4d59-aaf7-531f1033a58e
relation.isAuthorOfPublicationb9bbfe32-3dfe-4131-ad14-a4394008447f
relation.isAuthorOfPublication.latestForDiscoveryb9bbfe32-3dfe-4131-ad14-a4394008447f

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Vincent Laizé - SIMÃO_2019_BIOFACTORS_Author version.pdf
Size:
1.64 MB
Format:
Adobe Portable Document Format
Download

Collections

CCM2-Artigos (em revistas ou actas indexadas)
FCB2-Artigos (em revistas ou actas indexadas)