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BioMed Research International
Volume 2017 (2017), Article ID 2690402, 10 pages
Research Article

Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis

1Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
2Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, EPE, Lisbon Academic Medical Centre, Lisboa, Portugal
3EpiDoC Unit, CEDOC, NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal
4Musculoskeletal Diseases and Inflammation Research Group, Biomedicum Helsinki 1, Faculty of Medicine, Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland

Correspondence should be addressed to Inês P. Perpétuo

Received 1 October 2016; Accepted 4 January 2017; Published 13 February 2017

Academic Editor: Sadiq Umar

Copyright © 2017 Inês P. Perpétuo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 CD16 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.