Establishment of a novel screening system to isolate PTH-like osteogenic small compounds

建立新型PTH样成骨小化合物筛选体系

• 批准号: 24659824
• 负责人: NISHIMURA Riko
• 金额: $ 2.33万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659824/
• 关键词: PTH; 骨形成; スクリーニング; 骨芽細胞

Parathyroid hormone (PTH) has been shown to be a effective therapeutic agents for bone diseases such as osteoporosis. However, PTH has two major problems; high cost and limitation of term due to its possible side effect. Thus, we have attempted to contribute to development of screening systems that can allow us to explore the small compounds to mimic osteogenic action of PTH. We found that an osteoblastic cell line, SaOS2, is useful and suitable for the screening system. We also attempted to identify the target genes of PTH. Our data suggest that Wnt5a would be a target gene of PTH during bone formation. Our study suggest that a screening system in which we can determine the Wnt5a gene promoter activity would be helpful for developing the therapeutic bone forming small compounds.

甲状旁腺激素（Parathyroid hormone，PTH）是治疗骨质疏松等骨疾病的有效药物。然而，PTH有两个主要问题：高成本和由于其可能的副作用而导致的期限限制。因此，我们试图为筛选系统的开发做出贡献，该系统可以使我们探索模拟PTH成骨作用的小化合物。我们发现，成骨细胞系，SaOS 2，是有用的，适合的筛选系统。我们还试图确定PTH的靶基因。我们的数据表明，Wnt5a可能是骨形成过程中PTH的靶基因。我们的研究表明，一个筛选系统，我们可以确定Wnt5a基因启动子活性将有助于开发治疗性骨形成小化合物。

项目成果

Regulation of endochondral ossification by transcription factors

• DOI: 10.2741/4076
• 发表时间: 2012-06
• 期刊: Frontiers in Bioscience
• 作者: R. Nishimura;K. Hata;K. Ono;K. Amano;Yoko Takigawa;M. Wakabayashi;R. Takashima;T. Yoneda

Retinoic acid regulates commitment of undifferentiated mesenchymal stem cells into osteoblasts and adipocytes

• DOI: 10.1007/s00774-012-0385-x
• 发表时间: 2013-01-01
• 期刊: JOURNAL OF BONE AND MINERAL METABOLISM
• 影响因子: 3.3
• 作者: Hisada, Kunihiro;Hata, Kenji;Yoneda, Toshiyuki
• 通讯作者: Yoneda, Toshiyuki

The transcription factor FoxC1 regulates chondrogenesis together with Gli2 through induction ofPTHrP

转录因子 FoxC1 与 Gli2 一起通过诱导 PTHrP 调节软骨形成

• 发表时间: 2012
• 作者: Yoshida M;Hata K;Takashima R;Iseki S;Takano-Yamamoto T;Nishimura R;Yoneda T
• 通讯作者: Yoneda T

骨代謝調節機構におけるシグナル伝達と転写制御の役割

信号转导和转录控制在骨代谢调控机制中的作用

• 发表时间: 2013
• 期刊: 大阪大学歯学雑誌
• 作者: Hisada K;Hata K;Ichida F;Matsubara T;Orimo H;Nakano T;Yatani H;Nishimura R*;Yoneda T;西村理行
• 通讯作者: 西村理行

Regulation of Endochondral Ossification by Transcription Factor

转录因子对软骨内骨化的调节

• 发表时间: 2013
• 作者: Ikarashi M;Nakashima H;Kinoshita M;Sato A;Nakashima M;Miyazaki H;Nishiyama K;Yamamoto J;Seki S.;西村 理行;Riko Nishimura
• 通讯作者: Riko Nishimura