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This article is part of the supplement: 25th European Workshop for Rheumatology Research

Poster presentation

Gene expression profiling provides a link between high inflammatory synovitis and myofibroblast-like synoviocytes

TCG Timmer1, PV Kasperkovitz1, LGM van Baarsen1, P-P Tak2, TWJ Huizinga3, TCTM van der Pouw Kraan1 and CL Verweij1

Author Affiliations

1 Department of Molecular Cell Biology and Immunology, VUMC, Amsterdam, The Netherlands

2 Division of Clinical Immunology and Rheumatology, AMC, Amsterdam, The Netherlands

3 Department of Rheumatology, LUMC, Leiden, The Netherlands

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Arthritis Research & Therapy 2005, 7(Suppl 1):P67  doi:10.1186/ar1588


The electronic version of this article is the complete one and can be found online at:


Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd

Objective

The molecular pathogenesis of rheumatoid arthritis (RA) is still poorly understood. Given the heterogeneity in gene expression patterns and cellular distribution between RA synovial tissue, we determined whether this variability is also reflected at the level of fibroblast-like synoviocytes (FLS) cultured from those synovial tissues.

Methods

Gene expression profiles in FLS from 19 RA synovial tissues were analyzed using cDNA microarrays and hierarchical cluster analysis. To validate the subclassification, we performed prediction analysis and principal component analysis. Genes that differed significantly in expression between FLS cultures were selected using statistical analysis of microarrays. Real-time PCR was performed to validate microarray data. Immunostaining was applied to study the expression of the genes of interest in FLS and synovial tissues.

Results

Hierarchical clustering identified two main groups of FLS characterized by distinctive gene expression profiles. FLS from high inflammatory synovial tissues revealed increased expression of a transforming growth factor beta/ Activin A inducible gene program that is characteristic of myofibroblasts, a cell type that is considered to be involved in wound healing, whereas increased growth factor (IGF2/IGFBP5) production appears to constitute a characteristic feature of FLS derived of low inflammatory synovial tissues. The molecular feature that defines the myofibroblast-like phenotype is reflected as an increased proportion of myofibroblast-like cells in the heterogeneous FLS population. Myofibroblast-like cells are also found upon immunohistochemical analysis of synovial tissue.

Conclusion

The data support the notion that heterogeneity between synovial tissues is reflected in FLS as a stable trait, and provide evidence for a possible link between FLS behavior and the inflammatory status of RA synovium.