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

Autor: Ana M. Rodrigues, Raquel Campanilho-Marques, Joana Caetano-Lopes, I.P. Perpétuo, Helena Canhão, Mari Ainola, João Eurico Fonseca, Cristina Ponte
Přispěvatelé: Repositório da Universidade de Lisboa, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Centro de Estudos de Doenças Crónicas (CEDOC), Clinicum, University of Helsinki, Department of Medicine, HUS Internal Medicine and Rehabilitation
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Cathepsin K
Osteoclasts
lcsh:Medicine
Arthritis
Monocyte-Macrophage Precursor Cells
Monocytes
Bone remodeling
Arthritis
Rheumatoid
0302 clinical medicine
middle aged
318 Medical biotechnology
biology
adult
Intracellular Signaling Peptides and Proteins
General Medicine
Middle Aged
3. Good health
female
medicine.anatomical_structure
RANKL
Rheumatoid arthritis
monocyte
osteoclast
Female
Tumor necrosis factor alpha
Research Article
Adult
medicine.medical_specialty
Article Subject
General Biochemistry
Genetics and Molecular Biology
monocyte macrophage precursor cell
03 medical and health sciences
male
Osteoclast
Immunology and Microbiology(all)
Internal medicine
medicine
follow up
Humans
human
antagonists and inhibitors
TNF Receptor-Associated Factor 6
030203 arthritis & rheumatology
Cathepsin
General Immunology and Microbiology
Biochemistry
Genetics and Molecular Biology(all)
Tumor Necrosis Factor-alpha
business.industry
Monocyte
RANK Ligand
lcsh:R
medicine.disease
030104 developmental biology
Endocrinology
3121 General medicine
internal medicine and other clinical medicine
biology.protein
pathology
biosynthesis
business
metabolism
Follow-Up Studies
Zdroj: BioMed Research International, Vol 2017 (2017)
BioMed Research International
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
ISSN: 2314-6141
2314-6133
DOI: 10.1155/2017/2690402
Popis: 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 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.
This work was supported by Fundação para a Ciência e Tecnologia (SFRH/BD/70533/2010 to Inês P. Perpétuo) and by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp. (Merck_P08574 to João E. Fonseca).
Databáze: OpenAIRE
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