DKK1 expression by synovial fibroblasts in very early rheumatoid arthritis associates with lymphocyte adhesion in an in vitro flow co-culture system

Arthritis Research & Therapy
M JuarezAndrew D Filer

Abstract

Synovial fibroblasts play a key role in joint destruction and regulation of the inflammatory infiltrate in established rheumatoid arthritis (RA). The mechanisms by which this occurs in the earliest stages of RA are largely unknown. We investigated the role of Dickkopf-related protein 1 (DKK1) produced by synovial fibroblasts of patients with very early rheumatoid arthritis (VeRA). Fibroblasts were isolated from the disease-modifying anti-rheumatic drug-naive Birmingham early arthritis cohort of patients with new onset of clinically apparent arthritis and inflammatory symptoms of ≤12 weeks' duration, who at follow-up had either resolving arthritis or RA. Endothelial fibroblast co-cultures were formed using porous filters, and lymphocyte adhesion to co-cultures was assessed using phase-contrast microscopy. DKK1 gene expression and secretion were quantified by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Synovial fibroblasts from patients with VeRA expressed significantly higher levels of DKK1 messenger RNA than those from patients with resolving arthritis. A similar trend was observed for DKK1 protein secretion. In co-culture constructs, more DKK1 tended to be secreted in co-cultures...Continue Reading

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Citations

Apr 19, 2017·Clinical and Experimental Immunology·C WehmeyerA J Naylor
Aug 30, 2017·Annals of the Rheumatic Diseases·Andrew FilerHelen M McGettrick
Feb 20, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Juliane ColditzMartina Rauner
Apr 26, 2020·Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases·Alex Dario Cardona-RincónConsuelo Romero-Sánchez
Jul 6, 2016·Zeitschrift für Rheumatologie·K KleinS Gay
May 11, 2018·Scientific Reports·Emmanuel KarouzakisCaroline Ospelt
Jan 25, 2019·JCI Insight·Matthew J WoodCatharien Mu Hilkens
Apr 5, 2017·Journal of Immunology Research·Jing XueShuhong Chi
Jan 23, 2021·International Journal of Immunogenetics·Cyril DalmassoElisabeth Petit-Teixeira

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Methods Mentioned

BETA
biopsy
enzyme-linked immunosorbent assay

Software Mentioned

SPSS
Pro Plus
Image
PASW
Prism
GraphPad

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