1. Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitis
- Author
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Elsa Vieira-Sousa, Helena Canhão, Mari Ainola, João Eurico Fonseca, Cristina Ponte, Raquel Campanilho-Marques, Rita Raposeiro, Joana Caetano-Lopes, I.P. Perpétuo, Repositório da Universidade de Lisboa, Clinicum, and Department of Medicine
- Subjects
Male ,Pathology ,T-Lymphocytes ,lcsh:Medicine ,Osteoclasts ,UP-REGULATION ,Immunophenotyping ,Medicine ,Molecular Targeted Therapy ,lcsh:Science ,B-Lymphocytes ,Multidisciplinary ,Anti-Inflammatory Agents, Non-Steroidal ,Antibodies, Monoclonal ,Middle Aged ,3. Good health ,DIFFERENTIATION ,Phenotype ,Rheumatoid arthritis ,Antirheumatic Agents ,L-SELECTIN ,Cytokines ,Tumor necrosis factor alpha ,Female ,BONE-MINERAL DENSITY ,medicine.symptom ,Inflammation Mediators ,RECEPTOR ACTIVATOR ,NEUTROPHIL ,Research Article ,Adult ,medicine.medical_specialty ,Inflammation ,RADIOGRAPHIC PROGRESSION ,Bone resorption ,INFLAMMATION ,Humans ,Spondylitis, Ankylosing ,Bone Resorption ,Spondylitis ,Ankylosing spondylitis ,business.industry ,Gene Expression Profiling ,lcsh:R ,RANK Ligand ,medicine.disease ,Enthesis ,RHEUMATOID-ARTHRITIS ,3121 General medicine, internal medicine and other clinical medicine ,lcsh:Q ,Tumor Necrosis Factor Inhibitors ,business ,Biomarkers - Abstract
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, Introduction: 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.
- Published
- 2015