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Methotrexate and low-dose prednisolone downregulate osteoclast function by decreasing receptor activator of nuclear factor-κβ expression in monocytes from patients with early rheumatoid arthritis

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dc.contributor.authorPerpétuo, Inês Pedro
dc.contributor.authorCaetano-Lopes, joana
dc.contributor.authorRodrigues, Ana Maria
dc.contributor.authorCampanilho-marques, Raquel
dc.contributor.authorPonte, Cristina
dc.contributor.authorCanhao, Helena
dc.contributor.authorAinola, Mari-Mia
dc.contributor.authorFonseca, João Eurico
dc.date.accessioned2021-11-30T11:19:15Z
dc.date.available2021-11-30T11:19:15Z
dc.date.issued2017
dc.description© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.description.abstractObjective: Rheumatoid arthritis (RA) is a systemic, immune-mediated inflammatory disease that ultimately leads to bone erosions and joint destruction. Methotrexate (MTX) slows bone damage but the mechanism by which it acts is still unknown. In this study, we aimed to assess the effect of MTX and low-dose prednisolone (PDN) on circulating osteoclast (OC) precursors and OC differentiation in patients with RA. Methods: Patients with RA before and at least 6 months after MTX therapy were analysed and compared with healthy donors. A blood sample was collected in order to assess receptor activator of NF-κβ (RANK) ligand surface expression on circulating leucocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines and OC differentiation assays were performed. Results: Classical activation markers of monocytes and RANK increased in patients with RA at baseline, compared with control healthy donors, and after MTX and low-dose PDN (MTX+PDN) exposure they decreased to control levels. Although the number of OC was not different between groups, the percentage of resorbed area and the resorbed area per pit reduced after treatment. Serum soluble receptor activator of nuclear factor-kappa (RANKL) levels increased at baseline compared with healthy donors and normalised after therapy. Conclusion: Our results suggest that MTX+PDN play an important role in downregulating OC function, which we believe occurs through the decrease in RANK surface expression in monocytes.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e Tecnologia (SFRH/BD/70533/2010 to IPP) and by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp (Merck_P08574 to JEF).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationRMD Open. 2017 Jul 13;3(1):e000365pt_PT
dc.identifier.doi10.1136/rmdopen-2016-000365pt_PT
dc.identifier.eissn2056-5933
dc.identifier.urihttp://hdl.handle.net/10451/50213
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBMJ Publishing Group Ltd.pt_PT
dc.relation.publisherversionhttps://rmdopen.bmj.com/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectBonept_PT
dc.subjectDMARDpt_PT
dc.subjectMonocytespt_PT
dc.subjectOsteoclastpt_PT
dc.subjectRheumatoid arthritispt_PT
dc.titleMethotrexate and low-dose prednisolone downregulate osteoclast function by decreasing receptor activator of nuclear factor-κβ expression in monocytes from patients with early rheumatoid arthritispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberSFRH/BD/70533/2010
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F70533%2F2010/PT
oaire.citation.issue1pt_PT
oaire.citation.titleRMD Openpt_PT
oaire.citation.volume3pt_PT
oaire.fundingStreamSFRH
person.familyNamePerpétuo
person.familyNameCaetano-Lopes
person.familyNameRodrigues
person.familyNameCampanilho-Marques
person.familyNamePonte
person.familyNameCanhao
person.familyNameAinola
person.familyNameFonseca
person.givenNameInês
person.givenNameJoana
person.givenNameAna Maria
person.givenNameRaquel
person.givenNameCristina
person.givenNameHelena
person.givenNameMari
person.givenNameJoão
person.identifier386523
person.identifier405554
person.identifier405543
person.identifier.ciencia-idAE18-DA10-460C
person.identifier.ciencia-idFB1D-B9BA-5204
person.identifier.ciencia-id3713-901B-4493
person.identifier.ciencia-idF310-B85D-57C7
person.identifier.orcid0000-0001-7671-2539
person.identifier.orcid0000-0003-0310-4641
person.identifier.orcid0000-0003-2046-8017
person.identifier.orcid0000-0002-1894-8516
person.identifier.orcid0000-0002-3989-1192
person.identifier.orcid0000-0002-3239-2809
person.identifier.orcid0000-0003-2853-5851
person.identifier.orcid0000-0003-1432-3671
person.identifier.ridF-3643-2011
person.identifier.ridT-8035-2017
person.identifier.scopus-author-id16300521000
person.identifier.scopus-author-id57189499663
person.identifier.scopus-author-id6602393492
person.identifier.scopus-author-id6507004064
person.identifier.scopus-author-id7101983519
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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