Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitis
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/53425 |
Resumo: | Copyright: © 2015 Perpétuo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
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Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitisCopyright: © 2015 Perpétuo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedIntroduction: Ankylosing Spondylitis (AS) is characterized by excessive local bone formation and concomitant systemic bone loss. Tumor necrosis factor (TNF) plays a central role in the inflammation of axial skeleton and enthesis of AS patients. Despite reduction of inflammation and systemic bone loss, AS patients treated with TNF inhibitors (TNFi) have ongoing local bone formation. The aim of this study was to assess the effect of TNFi in the differentiation and activity of osteoclasts (OC) in AS patients. Methods: 13 AS patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. 25 healthy donors were recruited as controls. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and qRT-PCR for OC specific genes were performed. Results: RANKL+ circulating lymphocytes (B and T cells) and IL-17A, IL-23 and TGF-β levels were decreased after TNFi treatment. We found no differences in the frequency of the different monocyte subpopulations, however, we found decreased expression of CCR2 and increased expression of CD62L after TNFi treatment. OC number was reduced in patients at baseline when compared to controls. OC specific gene expression was reduced in circulating OC precursors after TNFi treatment. However, when cultured in OC differentiating conditions, OC precursors from AS TNFi-treated patients showed increased activity as compared to baseline. Conclusion: In AS patients, TNFi treatment reduces systemic pro osteoclastogenic stimuli. However, OC precursors from AS patients exposed to TNFi therapy have increased in vitro activity in response to osteoclastogenic stimuli.This work was supported by Fundação para a Ciência e Tecnologia (http://www.fct.pt/index.phtml.en) PhD grant (SFRH/BD/70533/2010) and in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp (http://www.merck.com/index.html - Merck_P08574). The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp.PLOSRepositório da Universidade de LisboaPerpétuo, Inês PedroRaposeiro, RitaCaetano-Lopes, JoanaVieira De Sousa, Elsa CristinaCampanilho-Marques, RaquelPonte, CristinaCanhao, HelenaAinola, MariFonseca, João Eurico2022-06-21T15:07:26Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/53425engPLoS One. 2015 Dec 16;10(12):e014465510.1371/journal.pone.01446551932-6203info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:59:11Zoai:repositorio.ul.pt:10451/53425Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:22.502841Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitis |
title |
Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitis |
spellingShingle |
Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitis Perpétuo, Inês Pedro |
title_short |
Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitis |
title_full |
Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitis |
title_fullStr |
Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitis |
title_full_unstemmed |
Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitis |
title_sort |
Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitis |
author |
Perpétuo, Inês Pedro |
author_facet |
Perpétuo, Inês Pedro Raposeiro, Rita Caetano-Lopes, Joana Vieira De Sousa, Elsa Cristina Campanilho-Marques, Raquel Ponte, Cristina Canhao, Helena Ainola, Mari Fonseca, João Eurico |
author_role |
author |
author2 |
Raposeiro, Rita Caetano-Lopes, Joana Vieira De Sousa, Elsa Cristina Campanilho-Marques, Raquel Ponte, Cristina Canhao, Helena Ainola, Mari Fonseca, João Eurico |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Perpétuo, Inês Pedro Raposeiro, Rita Caetano-Lopes, Joana Vieira De Sousa, Elsa Cristina Campanilho-Marques, Raquel Ponte, Cristina Canhao, Helena Ainola, Mari Fonseca, João Eurico |
description |
Copyright: © 2015 Perpétuo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z 2022-06-21T15:07:26Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/53425 |
url |
http://hdl.handle.net/10451/53425 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLoS One. 2015 Dec 16;10(12):e0144655 10.1371/journal.pone.0144655 1932-6203 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
PLOS |
publisher.none.fl_str_mv |
PLOS |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134594983788544 |