Open Access Research article

Functional analysis of an arthritogenic synovial fibroblast

Vassilis Aidinis1*, David Plows2, Sylva Haralambous2, Maria Armaka1, Petros Papadopoulos1, Maria Zambia Kanaki1, Dirk Koczan3, Hans Juergen Thiesen3 and George Kollias1*

Author Affiliations

1 Institute of Immunology, Biomedical Sciences Research Center 'Alexander Fleming', Athens, Greece

2 Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece

3 Institute of Immunology, University of Rostock, Rostock, Germany

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Arthritis Res Ther 2003, 5:R140-R157  doi:10.1186/ar749

Published: 14 March 2003

Abstract

Increasing attention has been directed towards identifying non-T-cell mechanisms as potential therapeutic targets in rheumatoid arthritis. Synovial fibroblast (SF) activation, a hallmark of rheumatoid arthritis, results in inappropriate production of chemokines and matrix components, which in turn lead to bone and cartilage destruction. We have demonstrated that SFs have an autonomous pathogenic role in the development of the disease, by showing that they have the capacity to migrate throughout the body and cause pathology specifically to the joints. In order to decipher the pathogenic mechanisms that govern SF activation and pathogenic potential, we used the two most prominent methods of differential gene expression analysis, differential display and DNA microarrays, in a search for deregulated cellular pathways in the arthritogenic SF. Functional clustering of differentially expressed genes, validated by dedicated in vitro functional assays, implicated a number of cellular pathways in SF activation. Among them, diminished adhesion to the extracellullar matrix was shown to correlate with increased proliferation and migration to this matrix. Our findings support an aggressive role for the SF in the development of the disease and reinforce the perspective of a transformed-like character of the SF.

Keywords:
fibroblast; gene expression; migration; rheumatoid arthritis; tumor necrosis factor