Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis
Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patient...
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Online Access: | http://dx.doi.org/10.1155/2017/2690402 |
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doaj-117b6d6d10ce4221baa333ba3382eded2020-11-24T21:37:12ZengHindawi LimitedBioMed Research International2314-61332314-61412017-01-01201710.1155/2017/26904022690402Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid ArthritisInês P. Perpétuo0Joana Caetano-Lopes1Ana Maria Rodrigues2Raquel Campanilho-Marques3Cristina Ponte4Helena Canhão5Mari Ainola6João E. Fonseca7Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, PortugalRheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, PortugalRheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, PortugalRheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, PortugalRheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, PortugalEpiDoC Unit, CEDOC, NOVA Medical School, Universidade Nova de Lisboa, Lisboa, PortugalMusculoskeletal Diseases and Inflammation Research Group, Biomedicum Helsinki 1, Faculty of Medicine, Institute of Clinical Medicine, University of Helsinki, Helsinki, FinlandRheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, PortugalObjective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. 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, in vitro OC differentiation assays, and qRT-PCR for OC specific genes was performed. Results. After TNFi therapy, patients had reduced RANKL surface expression in B-lymphocytes and the frequency of circulating classical CD14brightCD16− monocytes was decreased. Serum levels of sRANKL, sRANKL/OPG ratio, and CTX-I were reduced in RA patients after TNFi treatment. Moreover, after exposure to TNFi, osteoclast differentiation and activity were decreased, as well as the expression of TRAF6 and cathepsin K. Conclusion. We propose that TNFi arrests bone loss and erosion, through two pathways: direct reduction of osteoclast precursor numbers and inhibition of intracellular signaling pathways acting through TRAF6.http://dx.doi.org/10.1155/2017/2690402 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Inês P. Perpétuo Joana Caetano-Lopes Ana Maria Rodrigues Raquel Campanilho-Marques Cristina Ponte Helena Canhão Mari Ainola João E. Fonseca |
spellingShingle |
Inês P. Perpétuo Joana Caetano-Lopes Ana Maria Rodrigues Raquel Campanilho-Marques Cristina Ponte Helena Canhão Mari Ainola João E. Fonseca Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis BioMed Research International |
author_facet |
Inês P. Perpétuo Joana Caetano-Lopes Ana Maria Rodrigues Raquel Campanilho-Marques Cristina Ponte Helena Canhão Mari Ainola João E. Fonseca |
author_sort |
Inês P. Perpétuo |
title |
Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis |
title_short |
Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis |
title_full |
Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis |
title_fullStr |
Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis |
title_full_unstemmed |
Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis |
title_sort |
effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in rheumatoid arthritis |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2017-01-01 |
description |
Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. 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, in vitro OC differentiation assays, and qRT-PCR for OC specific genes was performed. Results. After TNFi therapy, patients had reduced RANKL surface expression in B-lymphocytes and the frequency of circulating classical CD14brightCD16− monocytes was decreased. Serum levels of sRANKL, sRANKL/OPG ratio, and CTX-I were reduced in RA patients after TNFi treatment. Moreover, after exposure to TNFi, osteoclast differentiation and activity were decreased, as well as the expression of TRAF6 and cathepsin K. Conclusion. We propose that TNFi arrests bone loss and erosion, through two pathways: direct reduction of osteoclast precursor numbers and inhibition of intracellular signaling pathways acting through TRAF6. |
url |
http://dx.doi.org/10.1155/2017/2690402 |
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