Suppression of early experimental osteoarthritis by in vivo delivery of the adenoviral vector-mediated NF-κBp65-specific siRNA

SummaryObjectiveThis study was to use adenoviral vector-mediated nuclear factor-κBp65 (NF-κBp65)-specific siRNA (Ad-siRNANF-κBp65) to suppress the progression of early osteoarthritis (OA) in rat model, and therefore to explore a new gene therapy for OA.MethodsReverse transcription polymerase chain reaction was performed to confirm the silencing effect of Ad-siRNANF-κBp65 in cultured rat chondrocytes. Transection of the medial collateral ligament plus partial medial meniscectomy was operated in the knee of rats to establish OA model. Histological analysis was made to assess the morphological change of cartilage and synovium, and enzyme-linked immunosorbent assay was made to measure the expression of cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), in synovial fluid. The silencing effect of Ad-siRNANF-κBp65 on NF-κBp65 in cartilage and synovium of knee was measured with Western blot and the activation of NF-κB was measured with electrophoretic mobility shift assays.ResultsAd-siRNANF-κBp65 can inhibit the activation of NF-κB and the expression of NF-κBp65 in cartilage and synovium of the knee, restrain the induction of IL-1β and TNF-α in synovial fluid, alleviate the inflammation of synovium and reduce the degradation of cartilage in early phase of experimental OA.ConclusionsAd-siRNANF-κBp65 can suppress the progression of the early experimental OA which suggests that Ad-siRNANF-κBp65 has potential to be a useful preventive and therapeutic agent for OA.