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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

2017-07-01Artigo científico Acesso aberto
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dc.contributor.authorCaetano-Lopes, Joana
dc.contributor.authorRodrigues, Ana Maria
dc.contributor.authorCampanilho-Marques, Raquel
dc.contributor.authorPonte, Cristina
dc.contributor.authorCanhão, Helena
dc.contributor.authorCanhão, Helena
dc.contributor.authorAinola, Mari
dc.contributor.authorFonseca, João Eurico
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.pblBMJ Publishing Group
dc.date.accessioned2017-12-11T23:40:43Z
dc.date.available2017-12-11T23:40:43Z
dc.date.issued2017-07-01
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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent9
dc.format.extent1119126
dc.identifier.doi10.1136/rmdopen-2016-000365
dc.identifier.issn2044-6055
dc.identifier.otherPURE: 3096341
dc.identifier.otherPURE UUID: b934e558-0946-4bc1-8cad-2a2f19f0d27b
dc.identifier.otherScopus: 85024374546
dc.identifier.otherPubMed: 28955481
dc.identifier.otherPubMedCentral: PMC5604603
dc.identifier.otherWOS: 000443681800016
dc.identifier.otherORCID: /0000-0003-1894-4870/work/67178258
dc.identifier.urihttp://www.scopus.com/inward/record.url?scp=85024374546&partnerID=8YFLogxK
dc.identifier.urlhttps://www.scopus.com/pages/publications/85024374546
dc.language.isoeng
dc.peerreviewedyes
dc.subjectBone
dc.subjectDMARD
dc.subjectMonocytes
dc.subjectOsteoclast
dc.subjectRheumatoid arthritis
dc.subjectRheumatology
dc.subjectImmunology
dc.subjectImmunology and Allergy
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 arthritisen
dc.typejournal article
degois.publication.issue1
degois.publication.titleRMD Open
degois.publication.volume3
dspace.entity.typePublication
person.familyNameCanhão
person.givenNameHelena
person.identifier379800
person.identifier.ciencia-id5A17-C6D9-DBC8
person.identifier.orcid0000-0003-1894-4870
person.identifier.ridC-9611-2018
person.identifier.scopus-author-id6602393492
rcaap.rightsopenAccess
relation.isAuthorOfPublicationc87f58c0-b53d-4321-9bd7-39554e6001b5
relation.isAuthorOfPublication.latestForDiscoveryc87f58c0-b53d-4321-9bd7-39554e6001b5

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