Gene therapy for osteochondral defect

骨软骨缺损的基因治疗

• 批准号: 13671516
• 负责人: WATANABE Shohei
• 金额: $ 2.3万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671516/
• 关键词: Gene therapy; Osteochondral injury; Adenovirus; FGF2; IL-4; Plasmid; IL4

1. To determine the therapeutic effect of FGF-2 mediated adenovirus vector on the osteochondral injury of the knee joints, AdCAsFGF-2 was administrated to the male Wister rats intravenously, in which knee joint osteochondral defect model was made by drilling with a surge-airtome. It was observed that cartilage repair was seen in the knee joints of rats with which were administrated AdCAsFGF-2 compared with rats injected with AxCAEGFP, control virus. Although there was the problem to induce the inflammation by AdCAsFGF-2, it seemed that local administration with vecotrs could be a therapeutic method for osteochondral injury.2. To examine the effect of IL-4 on matrix synthesis in chondrocytes under excessive mechanical stress in vitro. Mechanical stress for 16 hours significantly decreased levels of mRNA for both AGG and CII (p <0.01), but rat IL-4 at doses of 1 or 10 ng/ml recovered these levels (p <0.05). These findings suggested that IL-4 might prevent articular cartilage from damage caused by mechanical stress and therefore could be a useful therapeutic agent for treatment of arthritic disorders.3. Fibronectin is one of the major extracellular matrix components in synovium, and it plays a central role in cell-cell and cell-matrix interactions through ligation of cell surface integrins. In the present study, a 15 amino acid peptide derived from the carboxy-terminal 33-kD cell and heparin-binding domain of fibronectin (FN-C/H-II) suppressed established arthritis in mice, associated with reduced infiltration of inflammatory cells into the joint.

1.为探讨FGF-2介导的腺病毒载体对膝关节骨软骨损伤的治疗作用，将AdCAsFGF-2经静脉注射给雄性Wister大鼠，用冲击-空气刀钻孔造成膝关节骨软骨缺损模型。观察到，与注射AxCAEGFP（对照病毒）的大鼠相比，在施用AdCAsFGF-2的大鼠的膝关节中观察到软骨修复。尽管AdCAsFGF-2诱导炎症存在问题，但局部给予vecotrs似乎可以成为骨软骨损伤的一种治疗方法。2.研究IL-4对体外过度机械应力下软骨细胞基质合成的影响。16小时的机械应力显著降低AGG和CII的mRNA水平（p <0.01），但1或10 ng/ml剂量的大鼠IL-4恢复了这些水平（p <0.05）。提示IL-4可能对机械应力引起的关节软骨损伤具有保护作用，有望成为治疗关节炎的有效药物.纤连蛋白是滑膜中主要的细胞外基质成分之一，它通过连接细胞表面整合素在细胞-细胞和细胞-基质相互作用中起核心作用。在本研究中，一个15个氨基酸的肽来自羧基末端33 kD细胞和肝素结合结构域的纤连蛋白（FN-C/H-II）抑制建立关节炎小鼠，与减少浸润的炎性细胞进入关节。

项目成果

Imagawa T, Watanabe S, Katakura S, Boivin GP, Hirsch R.: "Gene transfer of a fibronectin peptide inhibits leukocyte recruitment and suppresses inflammation in mouse collagen-induced arthritis"Arthritis Rheum.. 46(4). 1102-1108 (2002)

Imakawa T、Watanabe S、Katakura S、Boivin GP、Hirsch R.：“纤连蛋白肽的基因转移抑制白细胞募集并抑制小鼠胶原诱导的关节炎中的炎症”Arthritis Rheum.. 46(4)。