The objective of the study was to determine the effects and the molecular background of interleukin-1 receptor antagonist (IL-1Ra) and vIL-10 double gene transfer into human synovial fibroblasts from patients with rheumatoid arthritis (RA) using the SCID mouse model for cartilage erosion in RA. RA synovial fibroblasts were transduced with retro- or adenoviruses encoding IL-1Ra and/or viral IL-10 (vIL-10). SCID mice were engrafted subcutaneously with IL-1Ra and vIL-10 transduced human rheumatoid synovial fibroblasts and normal cartilage. In parallel, gene expression analysis before and after gene transfer using RNA arbitrarily primed PCR in combination with cDNA array was performed. vIL-10 and IL-1Ra double gene transfer resulted in inhibition of cartilage invasion and degradation by RA synovial fibroblasts when compared with control transduced and nontransduced implants. Expression of key genes that were altered after double gene transfer were related to the activin pathway. The results demonstrate not only that virus-based gene transfer using a combination of two joint-protective genes is a feasible approach to inhibit cartilage degradation by activated RA synovial fibroblasts, but also that the underlying molecular effects include modulation of the activin pathway.
Bibliographical noteFunding Information:
This study was supported by grants of the German Academic Research Society (DFG Mu 1383/3-1, 1383/3-3, and Ku 1024/6-1), as well as by the Swiss National Foundation (32-64142.00). The authors wish to thank Birgit Riepl and Wibke Ballhorn for excellent technical assistance.
- Rheumatoid arhritis
- cDNA array