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

BMC Musculoskeletal Disorders

Matthew A Brown²  Malcolm Smith⁴  Simranpreet Kaur⁵  Helen Weedon⁴  Allison R Pettit³  Ran Duan¹  Gethin P Thomas² 

[1] The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Australia;The University of Queensland Diamantina Institute, Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102, Australia;Australia and University of Queensland Centre for Clinical Research, Royal Brisbane & Women’s Hospital Campus, Bowen Bridge Road, Herston, QLD 4029, Australia;Repatriation General Hospital, Daw Park, SA 5041, Australia;The University of Queensland Centre for Clinical Research, Brisbane, QLD 4029, Australia

关键词: Microarrays;    Gene expression;    MMP3;    Inflammation;    Spondyloarthritis;    Synovial membrane;    Ankylosing spondylitis;   

Others  :  1129044
DOI  :  10.1186/1471-2474-14-354

 received in 2013-06-03, accepted in 2013-12-05,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Thomas et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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