RNAi Silencing of IL-1β and TNF-α in the Treatment of Post-traumatic Arthritis in Rabbits.

Abstract

Post-traumatic arthritis is a secondary complication to severe joint trauma. With the disease progression, it may eventually lead to osteoarthritis in patients whose age is considerably younger than patients with traditional bone arthritis. The main objective of this study was to explore the feasibility of using lentiviral-mediated RNA interference silencing of IL-1β and TNF-α to treat post-traumatic arthritis in rabbits. About 48 New Zealand rabbits underwent bilateral knee joint surgery to stimulate traumatic arthritis. They were then randomly divided into four groups of 12 rabbits each. The histopathology of the cartilage was observed, and the changes were assessed by Mankin scoring. ELISA was used to detect the expression of IL-1β and TNF-α in the synovial fluid. (i) Compared with the control group, the transfection and co-transfected groups displayed reduced cartilage damage and speed of degeneration. The co-transfected group showed the greatest alleviation of symptoms. The Mankin score was statistically different (p<0.01). (ii) Compared with the control group, the expression of IL-1β or TNF-α was reduced in the respective transfection groups (p<0.01 in both groups) and IL-1β and TNF-α were reduced in the co-transfected group (p<0.01). The co-transfected group showed the lowest expression of the three experimental groups of both IL-1β and TNF-α (p<0.01). Lentivirus-mediated RNA interference can knock down the expression of IL-1β and TNF-α in joint fluids and, in a synergistic effect when two siRNAs are co-transfected, ease cartilage degeneration.