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

类风湿关节炎（RA）是一种慢性炎症性疾病，伴进行性关节牵伸，在我国有80多万人患有此病。骨关节炎（OA）也是最常见的全身性疾病之一，在不久的将来，随着老年人数量的增加，需要更有效的治疗方法。因此，我们关注NFκB对RA和OA发病过程中炎症因子或蛋白酶的调节作用。我们已经报道了NFκB在关节炎的调节中发挥重要作用，诱饵脱氧核苷酸（ODN）可以通过我们的原始hvj脂质体基因传递系统抑制NFκB的激活。在本研究中，我们制备了RA和OA的实验动物模型，以评估NFκB诱骗ODN对这两种关节炎的关节破坏的作用。我们发现NFκB诱饵ODN通过下调IL-Iβ和TNFα抑制大鼠胶原诱导关节炎（CIA）的恶化，并在猴子中证实了同样的结果。我们建立前交叉韧带横断（ACLT）大鼠作为OA模型。NFκB诱饵ODN对实验性关节炎也有一定的治疗作用。我们得出结论，针对NFκB的诱饵策略是治疗RA和OA的有效候选策略。NFκB诱骗ODN在RA患者关节中的临床应用将随本研究结果而定。

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.