Angiostatin gene transfer as an effective treatment strategy in murine collagen-induced arthritis
Angiostatin gene transfer as an effective treatment strategy in murine collagen-induced arthritis
复制标题
DOI：
10.1002/art.10113
复制
发表时间：
2002-03-01
影响因子：
--
通讯作者：
Kim, S
中科院分区：
文献类型：
--
作者：
Kim, JM;Ho, SH;Kim, S
客观的。确定人血管抑制素基因局部治疗鼠胶原诱导性关节炎（CIA）的疗效。方法。 DBA/1 小鼠用牛 H 型胶原蛋白进行免疫。在关节炎发作之前，将用表达血管抑制素的逆转录病毒载体或对照载体转导的NIH3T3成纤维细胞移植到膝腔中。根据血管翳形成和软骨破坏对膝关节关节炎的发生率进行组织学评估。对爪子的发红、肿胀和畸形进行宏观评估，并对白介素-1β 水平进行免疫学评估。使用抗 CD31 抗体通过免疫组织化学研究爪子和膝关节的血管生成并测量血管性血友病因子水平。结果。在移植了血管抑制素表达细胞的膝盖中，血管翳形成和软骨侵蚀显着减少。此外，注射血管抑制素基因的膝盖以下同侧爪子的CIA发病得到了显着预防。此外，血管抑制素基因转移抑制关节炎相关的血管生成。结论。膝关节局部产生血管抑制素不仅能够预防注射基因工程细胞的膝关节中 CIA 的发生，而且还能预防未注射基因工程细胞的同侧爪子的发生。这表明血管抑制素基因及其蛋白质的转移可能为治疗类风湿性关节炎提供一种新的、有效的方法。
Objective. To determine the efficacy of local therapy with human angiostatin gene in murine collagen-induced arthritis (CIA).Methods. DBA/1 mice were immunized with bovine type H collagen. Before the onset of arthritis, NIH3T3 fibroblasts, transduced with angiostatin-expressing retroviral vectors or control vectors, were transplanted into the knee cavity. The incidence of arthritis in the knee joints was evaluated histologically based on pannus formation and cartilage destruction. Paws were evaluated macroscopically for redness, swelling, and deformities and immunologically for levels of interleukin-1beta. Angiogenesis in paws and knee joints was studied by immunohistochemistry using anti-CD31 antibody and measurement of von Willebrand factor levels.Results. Pannus formation and cartilage erosion were dramatically reduced in knees transplanted with angiostatin-expressing cells. In addition, the onset of CIA in the ipsilateral paws below the knees injected with the angiostatin gene was significantly prevented. Furthermore, angiostatin gene transfer inhibited arthritis-associated angiogenesis.Conclusion. Local production of angiostatin in the knee was able to prevent the onset of CIA not only in the knee injected with genetically engineered cells, but also in the uninjected ipsilateral paw. This suggests that transfer of the angiostatin gene, and potentially also its protein, may provide a new, effective approach to the treatment of rheumatoid arthritis.