Protective Effect Of Lentivirus-mediated SiRNA Targeting ADAMTS-5on Cartilage Degradation In A Rat Model Of Osteoarthritis

Objective: The etiology of osteoarthritis (OA) is complex and multifaceted. Osteoarthritisis a chronic and progressive disease of the joints that is characterized by degradation ofarticular cartilage. A disintegrin and metalloproteinase with thrombopondinmotifs-5(ADAMTS-5) comprises is the major aggrecanase in cartilage. The aim of thisstudy was to evaluate the effect of ADAMTS-5knockdown on cartilage degradation.Materials and Methods: Rat articular chondrocytes were transfected withlentivirus-mediated ADAMTS-5siRNAs or with no-load lentivirus as the control. Thesuppression efficiency was measured using real-time polymerase chain reaction (RT-PCR)and western blotting. Then we chose the most effective siRNA1and constructed thelentivirus-mediated siRNA, targeting ADAMTS-5for stable transfection. OA was inducedin a male Sprague-Dawley rat model by performing anterior cruciate ligament transection(ACL-T) and partial medial meniscectomy (PM). The animals(number of80,weight of250–300g) received an intra-articular injection of no-load lentivirus or lentivirus-mediated ADAMTS-5siRNA1(20μL,1×108TU/mL).The progression of OA in all samples wascompared using Osteoarthritis Research Society International (OARIS) scores.Results: Compared with the control, ADAMTS-5gene suppression was nearly80%bysiRNA1in a monolayer culture of chondrocytes. The intra-articular injection oflentivirus-mediated ADAMTS-5siRNA1in vivo resulted in down-regulation ofADAMTS-5protein and improved OARIS scores (statistical significance p<0.05).Conclusions: A single injection of lentivirus-mediated ADAMTS-5siRNA induced thesuppression of degradation in articular cartilage. This method may provid a new therapy forhuman OA.