Fundamental Approach to Gene Therapy for Osteoarthritis

骨关节炎基因治疗的基本方法

• 批准号: 06671465
• 负责人: TAKAHASHI Katsuro
• 金额: $ 1.34万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671465/
• 关键词: Gene Therapy; Arthritis; Articular Cartilage; Transformong growth factor; Signal Transduction; gene therapy; arthritis; TGF-β; トランスホ-ミンググロースファクター; 細胞内情報伝達

Transforming growth factor (TGF-b) has been found to be a powerful multipotential regulator of the cellular activity of chondrocytes, and it is assumed to play a role in the repair of cartilage tissue. Delivery of TGT-b to the articular space by gene transfer offers a potential therapeutic modality. To determine the feasibility of using rat as a gene transfer system, intraarticular injections of the rat knee were performed. The pSV-b Galactosidase vector was injected intraarticulaly using lipofectin to ascertain whether gene delivery was possible with this approach. Synovial membrane and cartilage tissue were examined for lac-z expression histologically. High efficiency expression was observed in these tissues. And transgene expression could still be detected after 14 days.We also examined the signal transduction of TGF-b in chondrocytes and found that it was different from the other cells. TGF-b upregulated the induction of c-fos gene in chondrocytes. We are now determing the response element of c-fos gene for TGF-b by using a CAT assay method.Although, the delivery of TGF-b has not been successful, these results suggest the feasibility of gene therapy for osteoarthritis.

转化生长因子（TGF-β）已被发现是一个强大的多能调节软骨细胞的细胞活性，它被认为是在软骨组织的修复中发挥作用。通过基因转移将TGT-b递送至关节间隙提供了一种潜在的治疗方式。为了确定使用大鼠作为基因转移系统的可行性，进行了大鼠膝关节内注射。使用脂质体将pSV-b半乳糖苷酶载体关节内注射，以确定使用该方法是否可能进行基因递送。组织学检查滑膜和软骨组织的lac-z表达。在这些组织中观察到高效表达。我们还检测了软骨细胞中TGF-β的信号转导，发现它与其他细胞不同。TGF-β可上调软骨细胞c-fos基因的表达。我们目前正在用CAT法检测c-fos基因对TGF-β的反应元件，虽然TGF-β的导入还没有成功，但这些结果提示了骨关节炎基因治疗的可行性。

项目成果

T.Tsukazaki: "Effect of transforming growth factor-b on the insuin-like growth factor-I autocrine/paracrine axis in cultured rat articular chondrocytes." Exp Cell Res. 215. 9-16 (1994)

T.Tsukazaki：“转化生长因子-b 对培养的大鼠关节软骨细胞中胰岛素样生长因子-I 自分泌/旁分泌轴的影响。”

H.Yano,: "Evidence of c-fos expression implicating cell fate during palatal fusion in the rat." Develop Growth Different. (in press).

H.Yano：“c-fos 表达与大鼠腭融合过程中细胞命运相关的证据。”

T.Matsumoto: "Effects of interleukin-1b on insulin-like growth factor-I autocrine/paracrine axis in cultured rat articular chondrocytes." Annals of the Rheumatic Diseases. 53. 128-133 (1994)

T.Matsumoto：“IL-1b 对培养的大鼠关节软骨细胞中胰岛素样生长因子-I 自分泌/旁分泌轴的影响。”

H.Yano: "Evidence of c-fos expression implicating cell fate during palatal fusion in the rat." Develop Growth Different. (in press).

H.Yano：“c-fos 表达与大鼠腭融合过程中细胞命运相关的证据。”

T.Tsukazaki: "Expression of parathyroid hormone-related protein in rat aritcular cartilage." Calcif Tissue Int. 57. 196-200 (1995)

T.Tsukazaki：“大鼠关节软骨中甲状旁腺激素相关蛋白的表达。”