The effect of proteasome inhibitor on NF-κB signal path in a rat model of knee osteoarthritis / 中华骨科杂志

ABSTRACT

Objective To observe the effect of MG-132 on NF-κB signal path of cartilage and synovium in a rat model of knee osteoarthritis.Methods The rat models of knee osteoarthritis were established by performing anterior cruciate ligament amputation and partial medial meniscectomy.Totally 144 adult SD rats were randomly divided into 4 groupsMG-132 group,100 ml 0.007 g/L MG-132 solution was injected in to the knee joints of rat model 24 h after surgery; DMSO group,100 ml 0.1％ DMSO solution was injected 24 h after surgery; sham surgery group,merely the knee capsulotomy was performed and no solution was injected;control group,100 ml 0.007 g/L MG-132 solution was injected into the knee joints.The cartilage and synovium specimens were obtained at 2,4,12 weeks postoperatively.Pathomorphological observation was taken.The levels of NF-κB p65,I-κB,TNF-α and IL-1β at mRNA were detected by real-time PCR,and the activityof 20S proteasome was measured by fluorospectrophotometry.Resnlts The Mankin score of MG-132 groupwas lower than that of DMSO group.The Mankin scores of sham surgery and control groups were lower thanthose of MG-132 and DMSO groups with significant difference.The mRNA levels of NF-κB p65,IL-1 β,TNF-α of cartilage and synovium in MG-132 group were lower than those of DMSO group with significant differenceexcept for NF-κB p65 of synovium at 2 weeks and IL-1β of cartilage at 12 weeks.The mRNA levels of I-κB of cartilage at 2 weeks and I-κB of synovium at 4 weeks in MG-132 group were higher than those in DMSO group with statistical significance.Conclusion MG-132,the proteasome inhibitor,could postpone the progress of osteoarthritis through alleviating synovial inflammation and defending the articular cartilage.