Development of drugs for osteoporosis using transgenic mice

利用转基因小鼠开发治疗骨质疏松症的药物

• 批准号: 07557096
• 负责人: NODA Masaki
• 金额: $ 12.99万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557096/
• 关键词: bone; ligament; osteoporosis; osteoblast; transcription; promoter; type I collagen; transgenic animal; 遺伝子発現; 靭帯; BMP; 骨形成; スクリーニング系; 移植; ベータガラクトシダーゼ; 薬剤スクリーニング; 転写因子; トランスジェニックマウス; ベータガラトクシダーゼ; osteoblast; transcription; osteoclast /

We generated chloromphenicol acetyl transferase reporter construct using 1kb promoter region of rat osteocalcin gene and analyzed the transcriptional activity. Collagen (type I) is a major bone protein which comprises about 90% of the matrix activity in vivo. Betagalactosidase reporter construct was used for this collagen promoter study. Both osteocalcin and collagen promoter activity was confirmed in in vivo experiments. Furthemore, bone-forming agents, such as TGFbeta and BMP were found to be able to stimulate production of collagen and activation of the promoters. The transgenic animals containing collagen promoter fragment are useful for studying bone-related agents.

我们利用大鼠骨钙素基因的1 kb启动子区构建氯霉素乙酰转移酶报告基因，并分析其转录活性。胶原蛋白（I型）是一种主要的骨蛋白，其包含约90%的体内基质活性。β-半乳糖苷酶报告基因构建体用于该胶原启动子研究。在体内实验中证实了骨钙素和胶原促进剂的活性。此外，骨形成剂，如TGF β和BMP被发现能够刺激胶原蛋白的产生和启动子的激活。含有胶原启动子片段的转基因动物可用于骨相关因子的研究。

项目成果

Toshiyuki Kawa-uchi: "Messenger RNA Expression of the Genes Encoding Receptors for Bone Morphogenetic Protein (BMP) and Transforming Growth Factor-β (TGF-β) in the Cells from the Posterior Longitudinal Ligament in Cervical Spine" Endocrine. 5・3. 307-314 (

Toshiyuki Kawa-uchi：“颈椎后纵韧带细胞中骨形态发生蛋白 (BMP) 和转化生长因子-β (TGF-β) 受体基因的信使 RNA 表达”内分泌 5・3。 307-314（

T.Kawauchi, M.Noda et al.: "Messenger RNA Expression of the Genes Encoding Receptors for Bone Morphogenetic Protein(BMP)andTransforming Growth Factor-β(TGF-β) in the Cells from the Posterior Longitudinal Ligament in Cervical Spine" Endocrine. 5・3. 307-314

T.Kawauchi、M.Noda 等：“颈椎后纵韧带细胞中骨形态发生蛋白 (BMP) 和转化生长因子-β (TGF-β) 编码受体基因的信使 RNA 表达” .5・3.307-314

Y.Liu, H.Watanabe, Y.Yamada, E.Olson, A.Nifuji and M.Noda: "Overexpression of a single helix-loop-helix type transcription factor, scleraxis, enhances aggrecan gene expression in osteoblastic osteosarcoma ROS17/2.8 cells." Journal of Biological Chemistry.

Y.Liu、H.Watanabe、Y.Yamada、E.Olson、A.Nifuji 和 M.Noda：“单个螺旋-环-螺旋型转录因子 scleraxis 的过度表达可增强成骨细胞性骨肉瘤 ROS17/2.8 中聚集蛋白聚糖基因的表达

T.Kawa-uchi, K.Nose and M.Noda: "Fibroblast growth factor enhances expression of TGFbeta-stimulated-clone-22 gene in osteoblast-like cells." Endocrine. 3. 833-837 (1995)

T.Kawa-uchi、K.Nose 和 M.Noda：“成纤维细胞生长因子增强成骨细胞样细胞中 TGFbeta 刺激的克隆 22 基因的表达。”

A.Nifuji, M.Noda et al.: "Pertubation of BMP signaling in somitogenesis resulted in vertebral and rib malformation intheaxial skeletal formation." Journal of Bone and Mineral Research. 12・3. 332-342 (1997)

A. Nifuji、M. Noda 等人：“体节发生中的 BMP 信号传导导致轴向骨骼形成中的椎骨和肋骨畸形。”《骨与矿物研究杂志》12·3 (1997)。