Adenoviral Transfer Of P53 And Antisense C-MYC Gene Induce Apoptosis In Rheumatoid Synoviocytes And Reduces Inflammation In A Rabbit Model Of Arthritis

Background Rheumatoid arthritis is an autoimmune disease where the synovium of joint becomes thickened, hyperplasia, highly aggressive and infiltrated by inflammatory mononuclear cells. Synovial hyperplasia has been characterized as a tumor-like proliferation and is thought to be the major cause of destruction of joints. Because synoviocytes of RA may acquire properties generally associated with malignant tumor cells the therapeutic agents used to inhibit synovial fibroblast growth would be ideal for preventing synovitis and joint destruction. The mutant P53 and C-myc protooncogene is over-expressed in RA synovium and is thought to be involved in cellular activation, proliferation and transformation. Therefore, Regulation of P53 and C-MYC expression would be a novel strategy to inhibit growth and proliferation of RA-derived synovial cells. Of the vectors that are readily available, adenovirus is a highly effective vector both in vivo and in vitro, which infects a wide range of dividing and nondividing cells. Localizing the genes to the knee joint ensures maximum therapeutic effect within the area of application and reduces the risk of undesirable side effect.Objective The aim of this study was to establish the gene transfer method to treat RA through experiments in vivo and in vitro, and to address the feasibility of using adenoviral gene transfer of P53 and antisense C-MYC therapeutically to mediate apoptosis in RA synovium.Methods In vitro, adenoviral vectors were used to transfer P53 and antisense C-MYC cDNA into human RA and rabbit synovial fibroblasts in culture where apoptosis was evaluated using MTT, flowcytometry, TUNEL analysis and fluorescence microscopy.