Expression profiling in spondyloarthropathy synovial biopsies highlights changes in expression of inflammatory genes in conjunction with tissue remodelling genes

Thomas, Gethin P., Duan, Ran, Pettit, Allison R., Weedon, Helen, Kaur, Simranpreet, Smith, Malcolm, & Brown, Matthew A. (2013) Expression profiling in spondyloarthropathy synovial biopsies highlights changes in expression of inflammatory genes in conjunction with tissue remodelling genes. BMC Musculoskeletal Disorders, 14(354).

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Abstract

Background:

In the spondyloarthropathies, the underlying molecular and cellular pathways driving disease are poorly understood. By undertaking a study in knee synovial biopsies from spondyloarthropathy (SpA) and ankylosing spondylitis (AS) patients we aimed to elucidate dysregulated genes and pathways.

Methods

RNA was extracted from six SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry.

Results:

Four hundred and sixteen differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, B-cell associated, matrix catabolic, and metabolic pathways. Altered «myogene» profiling was also identified. The inflammatory mediator, MMP3, was strongly upregulated (5-fold) in AS/SpA samples and the Wnt pathway inhibitors DKK3 (2.7-fold) and Kremen1 (1.5-fold) were downregulated.

Conclusions:

Altered expression profiling in SpA and AS samples demonstrates that disease pathogenesis is associated with both systemic inflammation as well as local tissue alterations that may underlie tissue damaging modelling and remodelling outcomes. This supports the hypothesis that initial systemic inflammation in spondyloarthropathies transfers to and persists in the local joint environment, and might subsequently mediate changes in genes directly involved in the destructive tissue remodelling.

Impact and interest:

3 citations in Scopus
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2 citations in Web of Science®

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ID Code: 87641
Item Type: Journal Article
Refereed: Yes
Keywords: Ankylosing spondylitis, Gene expression, Inflammation, Microarrays, MMP3, Spondyloarthritis, Synovial membrane, complementary DNA, DKK3 protein, Kremen1 protein, oxidoreductase, stromelysin, unclassified drug, Wnt protein, article, B lymphocyte, catabolism, clinical article, controlled study, DNA probe, down regulation, enzyme activity, gene expression profiling, human, human tissue, immunohistochemistry, inflammatory gene, joint biopsy, mediator release, microarray analysis, muscle development, osteoarthritis, polymerase chain reaction, RNA extraction, RNA metabolism, spondyloarthropathy, synovium, tissue remodelling gene, validation process, Wnt signaling pathway, Adult, Aged, Female, Humans, Knee Joint, Male, Middle Aged, Regeneration, Spondylarthropathies, Young Adult
DOI: 10.1186/1471-2474-14-354
ISSN: 1471-2474
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2013 Thomas et al.
Copyright Statement: This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Deposited On: 23 Sep 2015 05:13
Last Modified: 21 Nov 2016 05:24

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