Gene transfer to synovial fibroblast: methods and evaluation in the SCID mouse model.

The use of gene transfer techniques has become of utmost importance both for the analysis of molecular pathways of rheumatic joint destruction and for the evaluation of novel therapeutic concepts to treat rheumatic diseases. However, gene transfer into synovial fibroblasts faces several challenges, which result mainly from the lack of specific surface markers and the low-proliferation rate of these cells. This chapter describes both nonviral and viral strategies of transferring gene constructs into synovial fibroblasts.

Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoid arthritis synovial fibroblasts.

The small ubiquitin-like modifier (SUMO)-1 is an important posttranslational regulator of different signaling pathways and involved in the formation of promyelocytic leukemia (PML) protein nuclear bodies (NBs). Overexpression of SUMO-1 has been associated with alterations in apoptosis, but the underlying mechanisms and their relevance for human diseases are not clear. Here, we show that the increased expression of SUMO-1 in rheumatoid arthritis (RA) synovial fibroblasts (SFs) contributes to the resistance of these cells against Fas-induced apoptosis through increased SUMOylation of nuclear PML protein and increased recruitment of the transcriptional repressor DAXX to PML NBs.