Effect Of Lentivirus-mediated RNA Interference Silencing IL-1 Type Ⅰ Receptor On MAPKs For Osteoarthritis Of The Knee In A Rat Model

BackgroundOsteoarthritis(OA) is one of the most common joint disorders which developing in chronic and degenerative way.It makes big influence not only in personal life but also in the economy of the whole society when the incidence of bone and joint disease is becoming higher in an aging society.OA is result of disequilibrium between cartilage matrix's degeneration and synthesis.The destruction of collagen in cartilage is OA 's main pathology.The high expression of matrix metalloproteinases(MMPs) may lead to the imbalance between degeneration and synthesis of chondrocyte's extracellular matrix(ECM).The effect of inflammation mediators,such as interleukin-1(IL-1),is necessary in the cartilage's degeneration,although cytokines is not enough.Mitogen-activated protein kinase(MAPKs) and nuclear factor-κB(NF-κB) signaling pathways are activated when IL-1βcombines with IL-1 R 1(IL-1 receptor type 1),which leading to the imbalance between tissue inhibitor of metalloproteinases-1(TIMP-1) and MMPs.The gene therapy of OA is becoming a focus recently and its possibility is supported by experiment.But the stability and long-term expression of exogenous gene in vivo has not solved yet.To observe the effect of lentivirus-mediated RNA interference silencing IL-1 R 1 on cartilage destruction and the expression of MAPKs in a rat model of OA which established by resecting of the anterior cruciate ligament(ACL) and anterior part of the right knee medial meniscus.PartⅠThe effect of lentivirus-mediated RNA interference silencing IL-1 R 1 on cartilage destruction for osteoarthritis of the knee in a ratmodelObjectives To observe the effect of lentivirus-mediated RNA interference silencing IL-1 R 1 on cartilage destruction in a rat model of OA,and to explore the role of IL-1 in OA.Material and methods Forty SD rats were randomly divided into four groups(A-1),each group:n =10).The rats(A-C group) were underwent unilateral anterior cruciate ligament-tomy and partial,excision of the medial meniscus.At day 7 and 9 after operation,the rats of group A were respectively received 40uL of lentivirus-mediated RNAi silencing IL-1 R 1 by intra-articular injection while the rats of group B were received lentivirus-mediated RNAi non-silencing IL-1 R 1 and the rats of group C were received saline.The rats of group D were taken for normal control. All rats were sacrificed four weeks after the surgery.The knees were harvested to observe macropathologic changes of the joint cartilage.Results Cartilage degradation in group A was milder than that in groups B and C(P＜0.05,P＜0.05),but was worse compared to group D(P＜0.05).There is no significant difference between group B and group C (P=0.547).Conclusions It works to establish OA rat model by resecting of ACL and anterior part of the medial meniscus.Lentivirus-mediated RNAi silencing IL-1 type 1 receptor can protect articular cartilage.PartⅡThe effect of MAPKs for osteoarthritis of the knee in a rat modelObjectives To observe the effect of lentivirus-mediated RNA interference silencing IL-1 R1 on the expression of MAPKs in a rat model of OA,and to explore the role of IL-1 and MAPKs in OA.Material and methods To get the knees of rats out of refrigerator and separate cartilage from knee joints.Levels of IL-1R 1,ERK1/2,JNK1/2 and p38 expression in the cartilage were detected by Western blot.Results Level of IL-1R 1 expression in cartilage in group A was significantly lower than that in groups BN C and D(P＜0.01,P＜0.01,P＜0.01).Level of p38 expression in cartilage in group A was lower than that in groups 13 and C(P＜0.05 P,＜0.05),but had no significant difference compared to group D(P＞0.05).Levels of ERK1/2 and JNK1/2 in cartilage in group A were lower than that in groups B and C(P＜0.05,P＜0.05),but was significantLy increased compared to group D(P＜0.05).Conclusions Lentivirus-mediated RNAi silencing IL-1 R 1 can protect articular cartilage and inhibit the expression of MAPKs,in particular,p38 protein was strongly inhibited.