• Inês P. Perpétuo
  • Joana Caetano-Lopes
  • Ana Maria Rodrigues
  • Raquel Campanilho-Marques
  • Cristina Ponte
  • Helena Canhão
  • Mari Ainola
  • João E. Fonseca

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 C D 14 b r i g h t 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.

Original languageEnglish
Article number2690402
Pages (from-to)Online
Number of pages10
JournalBioMed Research International
StatePublished - 13 Feb 2017

    Research areas

  • adult, antagonists and inhibitors, Arthritis, Rheumatoid, biosynthesis, female, follow up, human, male, metabolism, middle aged, monocyte, monocyte macrophage precursor cell, osteoclast, pathology

ID: 3096372