Functional analysis of an arthritogenic synovial fibroblast

Arthritis Research & Therapy

Vassilis Aidinis¹  David Plows³  Sylva Haralambous³  Maria Armaka¹  Petros Papadopoulos¹  Maria Zambia Kanaki¹  Dirk Koczan²  Hans Juergen Thiesen²  George Kollias¹ 

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

[2] Institute of Immunology, University of Rostock, Rostock, Germany

[3] Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece

关键词: tumor necrosis factor;    rheumatoid arthritis;    migration;    gene expression;    fibroblast;   

Others  :  1101389
DOI  :  10.1186/ar749

 received in 2002-10-01, accepted in 2003-02-20,  发布年份 2003

【 摘 要 】

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.

【 授权许可】

   
2003 Aidinis et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

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