Gene therapy for osteochondral defect

1.为确定成纤维细胞生长因子-2介导腺病毒载体对膝关节骨软骨损伤的治疗作用，将AdCAsFGF-2静脉注射给雄性Wister大鼠，用电涌喷雾器钻探造成大鼠膝关节骨软骨缺损模型。与注射AxCAEGFP的对照组相比，注射AdCAsFGF2的大鼠膝关节有明显的软骨修复。结论：1.虽然AdCAsFGF-2存在诱导炎症的问题，但维库曲斯局部给药可能是治疗骨软骨损伤的一种方法。探讨IL-4对体外高机械应力下软骨细胞基质合成的影响。机械应激16小时显著降低AGG和CII的mRNA水平(p&lt；0.01)，而1或10 ng/ml剂量的大鼠IL-4则恢复到这一水平(p&lt；0.05)。这些结果提示，IL-4可能对机械应力引起的关节软骨损伤有保护作用，有望成为治疗关节紊乱的有效药物。纤维连接蛋白是滑膜细胞外基质的主要成分之一，通过连接细胞表面整合素，在细胞与细胞、细胞与基质的相互作用中发挥重要作用。在本研究中，从33-kD细胞的羧基末端和纤维连接蛋白的肝素结合区(FN-C/H-II)获得的15个氨基酸的多肽抑制了小鼠已建立的关节炎，与减少炎症细胞对关节的渗透有关。

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.