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This article is part of the supplement: Fourth International Synovitis Workshop

Open Badges Meeting abstract

Activation of Synovial Fibroblasts in Rheumatoid Arthritis

Steffen Gay, Thomas Pap, Michael Nawrath, Juliane K Franz and Renate E Gay

Author Affiliations

University Hospital, Zürich, Switzerland

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Arthritis Res 2000, 1(Suppl 1):S19-201  doi:10.1186/ar33

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

Published:15 November 1999

© 2000 Current Science Ltd

Full text

Activation of synovial fibroblasts (SF) by upregulation of proto-oncogenes is thought to play a major role in rheumatoid joint destruction. To explore distinct signaling pathways in this activation we used retroviral gene transfer in the SCID mouse model. Specifically, we transferred dominant negative (dn) mutants, such as dn Raf-1 and dn c-myc to inhibit the Ras-Raf-MAPK cascade as well as the cascade involving myc. FLAG-tagged constructs used in this study were cloned into the retroviral vector LXSN. The data show that both Raf- as well as myc-dependent pathways contribute to the activation of synovial fibroblasts in RA.

Since mutations in PTEN have been described in cancer and associated with their invasiveness we studied the expression of this novel tumor-suppressor in RA. Although, no mutations of PTEN could be detected in RA synovium, only 40% of cultured RA-SF expressed PTEN, and a down-regulation was observed at sites of invasion into cartilage. These findings suggest that endogenous or autocrine down-regulation of this tumor-suppressor may contribute to the invasive behavior of RA-SF by maintaining their aggressive phenotype at sites of cartilage destruction in RA. Most interestingly, the same SF found at these sites are also the major producers of interleukin-16, a strong chemoattractant for CD4+ cells.


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