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

类风湿性关节炎(RA)是一种进行性关节牵张的慢性炎症性疾病，我国有80多万人患有类风湿关节炎。骨关节炎也是最常见的全身疾病之一，在不久的将来，随着老年人口的增加，需要更有效的治疗方法。因此，我们重点研究了核因子κB对参与类风湿关节炎和骨性关节炎发病的炎性细胞因子或蛋白水解酶的调节作用。我们已经报道了核因子κB在关节炎的调节中起重要作用，诱骗脱氧核苷酸可以抑制我们原有的带有hvJ-κ的基因递送系统激活的核因子DNA B。在本研究中，我们制备了类风湿性关节炎和骨性关节炎的实验动物模型，以评价核因子κB诱骗寡核苷酸对关节破坏的疗效。我们发现，核因子κB诱骗寡核苷酸通过下调IL-Iβ和肿瘤坏死因子α的表达来抑制大鼠胶原诱导性关节炎的恶化，并证实了在猴子中的相同结果。建立大鼠前交叉韧带切断(ACLT)模型。核因子κB诱骗寡核苷酸对实验性关节炎也有一定的治疗作用。我们的结论是，针对NFκB的诱骗策略是治疗类风湿关节炎和骨关节炎的有效候选药物。在我们的结果之后，核因子κB诱骗寡核苷酸在RA患者关节中的临床应用将会跟随我们的结果。

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.