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

针对类风湿性关节炎和骨关节炎进行性关节破坏的基因疗法

基本信息

  • 批准号:
    13470310
  • 负责人:
  • 金额:
    $ 8.96万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    2001
  • 资助国家:
    日本
  • 起止时间:
    2001 至 2002
  • 项目状态:
    已结题

项目摘要

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.
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。

项目成果

期刊论文数量(54)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Nakase T, Tomita T, et al.: "Involvement of BMP-2 signaling in a cartilage cap in osteochondroma"J Orthop Res. 19. 1085-1088 (2001)
Nakase T、Tomita T 等人:“骨软骨瘤软骨帽中 BMP-2 信号传导的参与”J Orthop Res。
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    0
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Tomita T, et al.: "Differentiation of monocytes into multinucleated giant bone-resorbing cells : two-step differentiation induced by nurse-like"Arthritis Res.. 3. 306-310 (2001)
Tomita T等人:“单核细胞分化为多核巨型骨吸收细胞:护士样诱导的两步分化”Arthritis Res.. 3. 306-310 (2001)
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    0
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Nakase T, Miyaji T, Kuriyama K, Tamai N, Horiki M, Tomita T, Myoui A, Shimada K, Yoshikawa H.: "Immunohistochemical detection of parathyroid hormone-related peptide. Indian hedgehog, and patched in the process of endochondral ossification in the human."Hi
Nakase T、Miyaji T、Kuriyama K、Tamai N、Horiki M、Tomita T、Myoui A、Shimada K、Yoshikawa H.:“甲状旁腺激素相关肽的免疫组织化学检测。印度刺猬,以及软骨内骨化过程中的补丁”
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    0
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Tanaka S, Tomita T, Yoshikawa H. et al.: "Novel autoantibodies to pituitary gland specific factor 1a in patients with rheumatoid arthritis"Rheumatology. 42(2). 353-356 (2003)
Tanaka S、Tomita T、Yoshikawa H. 等人:“类风湿性关节炎患者垂体特异性因子 1a 的新型自身抗体”风湿病学。
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    0
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Tomita T, Nakase T, Yoshikawa H. et al.: "Expression of extracellular matrix metalloproteinase inducer and enhancement of the production of matrix metalloproteinases in rheumatoid arthritis"Arthritis Rheum. 46(2). 373-378 (2002)
Tomita T、Nakase T、Yoshikawa H.等人:“类风湿性关节炎中细胞外基质金属蛋白酶诱导物的表达和基质金属蛋白酶产生的增强”关节炎大黄。
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SUGAMOTO Kazuomi其他文献

SUGAMOTO Kazuomi的其他文献

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{{ truncateString('SUGAMOTO Kazuomi', 18)}}的其他基金

Construction of a data base for 3D kinematics of all motion of all human joints.
构建所有人体关节所有运动的 3D 运动学数据库。
  • 批准号:
    22300204
  • 财政年份:
    2010
  • 资助金额:
    $ 8.96万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)

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创伤后和代谢型骨关节炎的免疫调节基因治疗策略
  • 批准号:
    445209
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Assessment of combinatorial gene therapy for the treatment of Osteoarthritis
组合基因疗法治疗骨关节炎的评估
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    9284382
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    2015
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治疗早期和晚期骨关节炎的组合基因疗法
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    301198
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    2013
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    Fellowship Programs
In Vivo Gene Therapy for Treatment of Osteoarthritis
治疗骨关节炎的体内基因疗法
  • 批准号:
    7913900
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In Vivo Gene Therapy for Treatment of Osteoarthritis
治疗骨关节炎的体内基因疗法
  • 批准号:
    8300235
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    2010
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颞下颌关节骨关节炎的分子机制及退化软骨的基因治疗
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    14571843
  • 财政年份:
    2002
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颞下颌关节骨关节炎的基因治疗
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使用 AAV 载体进行骨关节炎基因治疗。
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    12671434
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    2000
  • 资助金额:
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Fundamental Approach to Gene Therapy for Osteoarthritis
骨关节炎基因治疗的基本方法
  • 批准号:
    06671465
  • 财政年份:
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