title: Expression profiling in spondyloarthropathy synovial biopsies highlights changes in expression of inflammatory genes in conjunction with tissue remodelling genes.
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.
authors: The University of Queensland Diamantina Institute, Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102, Australia. gethin.thomas@uq.edu.au.
authors: Gethin P
authors: GP
authors: Thomas
authors: Ran
authors: R
authors: Duan
authors: Allison R
authors: AR
authors: Pettit
authors: Helen
authors: H
authors: Weedon
authors: Simranpreet
authors: S
authors: Kaur
authors: Malcolm
authors: M
authors: Smith
authors: Matthew A
authors: MA
authors: Brown
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007719:Knee Joint / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012038:Regeneration / Q000235:genetics; D025242:Spondylarthropathies / Q000209:etiology / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism*; D055815:Young Adult