title: Rheumatoid arthritis bone fragility is associated with upregulation of IL17 and DKK1 gene expression.
abstract: 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.
authors.affiliation: Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, Lisbon, 1649-028, Portugal, jribeirolopes@gmail.com.
authors.forename: Joana
authors.initials: J
authors.lastname: Caetano-Lopes
authors.forename: Ana
authors.initials: A
authors.lastname: Rodrigues
authors.forename: Ana
authors.initials: A
authors.lastname: Lopes
authors.forename: Ana C
authors.initials: AC
authors.lastname: Vale
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pitts-Kiefer
authors.forename: Bruno
authors.initials: B
authors.lastname: Vidal
authors.forename: Inês P
authors.initials: IP
authors.lastname: Perpétuo
authors.forename: Jacinto
authors.initials: J
authors.lastname: Monteiro
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: Maria F
authors.initials: MF
authors.lastname: Vaz
authors.forename: Ara
authors.initials: A
authors.lastname: Nazarian
authors.forename: Helena
authors.initials: H
authors.lastname: Canhão
authors.forename: João E
authors.initials: JE
authors.lastname: Fonseca
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001862:Bone Resorption / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics*; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D010024:Osteoporosis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome; D015854:Up-Regulation; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000096:biosynthesis / Q000097:blood
chemical_list: C501126:DKK1 protein, human; C498622:DKK2 protein, human; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D020381:Interleukin-17; C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D011518:Proto-Oncogene Proteins; C491119:WNT10B protein, human; D051153:Wnt Proteins; D051176:beta Catenin
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