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Rheumatoid Arthritis Bone Fragility Is Associated With Upregulation of IL17 and DKK1 Gene Expression

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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.

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The authors state that they have no conflict of interest.

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Authors and Affiliations

  1. Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, Lisbon, 1649-028, Portugal

    Joana Caetano-Lopes, Ana Rodrigues, Ana Lopes, Bruno Vidal, Inês P. Perpétuo, Helena Canhão & João E. Fonseca

  2. Rheumatology and Bone Metabolic Diseases Department, Lisbon Academic Medical Centre, Lisbon, Portugal

    Ana Rodrigues, Helena Canhão & João E. Fonseca

  3. Department of Mechanical Engineering, Instituto Superior Técnico, ICEMS, Lisbon, Portugal

    Ana C. Vale & Maria F. Vaz

  4. Center for Advanced Orthopaedic Studies, Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Michael A. Pitts-Kiefer & Ara Nazarian

  5. Orthopaedics Department, Lisbon Academic Medical Centre, Lisbon, Portugal

    Jacinto Monteiro

  6. Department of Medicine, ORTON Orthopaedic Hospital of the Invalid Foundation, COXA Hospital for Joint Replacement, Helsinki University Central Hospital and University of Helsinki, Hensinki and Tampere, Finland

    Yrjö T. Konttinen

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  1. Joana Caetano-Lopes
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  2. Ana Rodrigues
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  11. Ara Nazarian
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  12. Helena Canhão
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  13. João E. Fonseca
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Corresponding author

Correspondence to Joana Caetano-Lopes.

Additional information

Joana Caetano-Lopes, Ana Rodrigues, Helena Canhão, and João E Fonseca contributed equally.

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Caetano-Lopes, J., Rodrigues, A., Lopes, A. et al. Rheumatoid Arthritis Bone Fragility Is Associated With Upregulation of IL17 and DKK1 Gene Expression. Clinic Rev Allerg Immunol 47, 38–45 (2014). https://doi.org/10.1007/s12016-013-8366-y

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  • DOI: https://doi.org/10.1007/s12016-013-8366-y

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