Gene Therapy against the Progressive Joint Destruction of Rheumatoid Arthritis and Osteoarthritis

类风湿性关节炎（Rheumatoid Arthritis，RA）是一种进行性关节紊乱的慢性炎症性疾病，我国有80多万人患有RA。骨关节炎（Osteoarthritis，OA）也是最常见的全身性疾病之一，随着老年人数量的增加，需要更有效的治疗方法。因此，我们将研究重点放在NFκB对RA和OA发病机制中的炎性细胞因子或蛋白酶的调控上。NFκB在关节炎的发病机制中起重要作用，而诱骗性脱氧核苷酸（decoy deoxynucleotide，ODN）可通过HVJ脂质体基因传递系统抑制NFκB的活化。本研究通过制备类风湿关节炎和骨关节炎动物模型，观察NFκB B圈套ODN对类风湿关节炎和骨关节炎关节破坏的影响。NFκB B decoy ODN通过下调IL-1 β和TNFα的表达，抑制大鼠胶原诱导性关节炎（CIA）的恶化，并证实了NFκB decoy ODN对猴CIA的抑制作用。建立大鼠前交叉韧带横断（ACLT）的OA模型。NFκB decoy ODN对实验性关节炎也有一定的治疗作用。结论：针对NFκB的诱骗策略是治疗RA和OA的有效方法。NFκB B诱骗ODN在类风湿关节炎中的临床应用有待进一步研究。

Rheumatoid Arthritis(RA) is a chronic inflammatory disease with the progressive joint distraction, from which more than eight hundred thousands people are suffered in our country. Osteoarthritis(OA) is also one of the most common general disease, and the more effective therapy should be needed when the number of the elderly people will increase in the near future. So we focused on NFκB to modulate the inflammatory cytokines or proteinase which are involved in the pathogenesis of RA and OA. We have already reported that NFκB plays an important role in a regulation of arthritis and decoy deoxynucleotide(ODN) can suppress the activation of NFκB by our original gene delivery system with HVJ-lipoisome. In This investigation, we prepared the experimental animal model of RA and OA to evaluate the efficacy of NFκB decoy ODN against the joint destruction of these arthritis. We showed NFκB decoy ODN suppressed the deterioration of collagen-induced arthritis(CIA) in rats via down-regulation of IL-Iβ and TNFα, and also confirmed the same results with CIA in monkeys. As the OA model, we established the rats with anterior cruciate ligament transection(ACLT). NFκB decoy ODN was also effective to the experimental arthritis. We concluded That the decoy strategy against NFκB is an effective therapeutic candidate for RA and OA. The clinical application of NFκB decoy ODN to the joints of RA patients will be following after these our results.