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Ankylosing Spondylitis Patients Have Impaired Osteoclast Gene Expression in Circulating Osteoclast Precursors

2017-01Artigo científico Acesso aberto
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dc.contributor.authorPerpétuo, Inês P
dc.contributor.authorCaetano-Lopes, Joana
dc.contributor.authorVieira-Sousa, Elsa
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 E
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.pblFrontiers Media
dc.date.accessioned2018-03-12T23:14:50Z
dc.date.available2018-03-12T23:14:50Z
dc.date.issued2017-01
dc.description.abstractINTRODUCTION: Ankylosing spondylitis (AS) is typically characterized by focal bone overgrowth and also by systemic bone loss. We hypothesize that the increased osteoproliferation found in AS might be partially due to reduced ability of osteoclast precursors (OCPs) to differentiate into osteoclasts (OCs). Therefore, our aim was to characterize bone remodeling and pro-osteoclastogenesis inflammatory environment, monocytes' phenotype, andin vitroosteoclast differentiation in AS patients. METHODS: Patients with active AS without any ongoing therapy and age- and gender-matched healthy donors were recruited. Receptor activator of nuclear factor-κβ (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations were assessed. Quantification of serum levels of bone turnover markers and cytokines,in vitroOC differentiation assay and quantitative reverse transcription real-time PCR for OC-specific genes were performed. RESULTS: Pro- and anti-inflammatory cytokine serum levels were higher in AS patients than in controls. RANKL neutrophil expression was higher in AS patients when compared to healthy donors, but CD51/CD61 expression was lower in the classical monocyte subpopulation. Concerning osteoclastogenesis, we found no differences in thein vitroosteoclast differentiating potential of these cells when compared to healthy donors. However, we observed low expression of CSF1R, RANK, and NFATc1 in AS OCPs. CONCLUSION: Despite the high levels of pro-inflammatory cytokines present in AS patients, no differences in the number of OC or resorbed area were found between AS patients and healthy donors. Moreover, we observed that OCPs have low OC-specific gene expression. These findings support our hypothesis of an impaired response of OCPs to pro-osteoclastogenic stimuliin vivoin AS patients.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent9
dc.format.extent3740745
dc.identifier.doi10.3389/fmed.2017.00005
dc.identifier.issn2296-858X
dc.identifier.otherPURE: 3694890
dc.identifier.otherPURE UUID: 999b301d-4ac0-4243-8482-1f3c7e2089c9
dc.identifier.otherPubMed: 28191455
dc.identifier.otherPubMedCentral: PMC5269449
dc.identifier.otherWOS: 000407081600001
dc.identifier.otherScopus: 85058050969
dc.identifier.otherORCID: /0000-0003-1894-4870/work/67178282
dc.identifier.urihttp://hdl.handle.net/10362/32374
dc.language.isoeng
dc.peerreviewedyes
dc.subjectCSF1R
dc.subjectNFATc1
dc.subjectRANK
dc.subjectankylosing spondylitis
dc.subjectgene expression
dc.subjecthumans
dc.subjectmonocytes
dc.subjectosteoclasts
dc.titleAnkylosing Spondylitis Patients Have Impaired Osteoclast Gene Expression in Circulating Osteoclast Precursorsen
dc.typejournal article
degois.publication.titleFrontiers in medicine
degois.publication.volume4
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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