Abstract
We recently cloned Synoviolin, a transmembrane protein, by immunoscreening from the human cDNA library of rheumatiod synovial cells (RSCs) using anti-RSC antibodies. Synoviolin was highly expressed in rhuematioid synovial fibroblast cells. The mice overexpressing Synoviolin developed spontaneous arthropathy. Conversely, synoviolin+/- mice were resistant to collagen-induced arthritis. These results indicate that it is important for the prevention of arthritis to reduce the amount of Synoviolin. We thus analyzed the transcriptional regulation of Synoviolin promoter and identified that an Ets binding site (EBS) was crucial for the transcription of Synoviolin in vitro and in vivo. Furthermore, to investigate the effect of downregulation of Synoviolin in RSCs, we transfected the EBS decoy oligodeoxynucleotide (ODN) or Synoviolin antisense ODN into RSCs and carried out a proliferation assay using Alamar blue reagent, which resulted in the repression of proliferation activity through the suppression of Synoviolin expression. Our results suggest that the EBS decoy ODN provides a new therapeutic approach for the treatment of arthritis.
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