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Rheumatoid Arthritis Bone Fragility Is Associated With Upregulation of IL17 and DKK1 Gene Expression.
MedLine Citation:
PMID:  23546988     Owner:  NLM     Status:  Publisher    
Our aim was to compare bone gene expression in rheumatoid arthritis (RA) and primary osteoporosis (OP) patients. Secondary aims were to determine the association of gene expression of the Wnt/β-catenin signaling pathway with inflammatory cytokines in the bone microenvironment and to assess the serum levels of Wnt/β-catenin proteins in both groups. RA patients referred for hip replacement surgery were recruited. Primary OP patients were used as controls. Gene expression of Wnt pathway mediators, matrix proteins, and pro-inflammatory cytokines were analyzed in bone samples. Bone turnover markers, inflammatory cytokines, and Wnt mediators were measured in serum. Twenty-two patients were included: 10 with RA and 12 with primary OP. The expressions of Wnt10b (p = 0.034), its co-receptor LRP6 (p = 0.041), and its negative regulator DKK1 (p = 0.008) were upregulated in RA bone. IL17 gene expression in bone was upregulated in RA patients (p = 0.031) and correlated positively with Wnt10b (r = 0.810, p = 0.015), DKK2 (r = 0.800, p = 0.010), and RANKL/OPG ratio (r = 0.762, p = 0.028). DKK2 (p = 0.04) was significantly decreased in RA serum compared with primary OP. In conclusion, bone fragility in RA patients is induced by an unbalanced bone microenvironment and is associated with a specific gene expression pattern, namely, the upregulation of IL17 and DKK1, suggesting that the modulation of these two pathways might prevent RA systemic bone loss.
Joana Caetano-Lopes; Ana Rodrigues; Ana Lopes; Ana C Vale; Michael A Pitts-Kiefer; Bruno Vidal; Inês P Perpétuo; Jacinto Monteiro; Yrjö T Konttinen; Maria F Vaz; Ara Nazarian; Helena Canhão; João E Fonseca
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-4-2
Journal Detail:
Title:  Clinical reviews in allergy & immunology     Volume:  -     ISSN:  1559-0267     ISO Abbreviation:  Clin Rev Allergy Immunol     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-4-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9504368     Medline TA:  Clin Rev Allergy Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, Lisbon, 1649-028, Portugal,
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