Regulation of osteoblastic differentiation by the ubiquitin-proteasome pathway and novel induction of bone formation

泛素蛋白酶体途径调节成骨细胞分化和新的骨形成诱导

• 批准号: 23659865
• 负责人: TAMURA Masato
• 金额: $ 2.25万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659865/
• 关键词: プロテアソーム阻害剤; Bortezomib; 骨芽細胞; Wntシグナル; ユビキチンープロテアソーム系; プロテオソーム; ユビキチン; 骨形成; プロテアソーム

Recent observations suggest that bone metabolism is regulated by the ubiquitin-proteasome pathway, and certain proteasome inhibitor has been reported to induce differentiation of osteoblasts in vitro and in vivo. In this study, we show that bortezomib induces osteoblastic differentiation and inhibits myogenic differentiation in C2C12 cells in culture. Bortezomib inhibits ubiquitin proteasome pathway to degradation of osteogenic transcriptional factor Runx2 and the function of proteasome in controlling degradation of signaling molecules in osteoblast differentiation. Bortezomib could not alter transcriptional activities of beta-catenin dependent reporter and canonical Wnt signaling target gene expression. We also demonstrated that inhibition of certain ubiquitin ligase (E3) up-regulates the differentiation of osteoblasts.

最近的观察结果表明，骨代谢受泛素 - 蛋白酶体途径调节，据报道某些蛋白酶体抑制剂在体外和体内诱导成骨细胞的分化。在这项研究中，我们表明硼替佐米诱导成骨细胞分化并抑制培养物中C2C12细胞中的肌源分化。硼替佐米抑制泛素蛋白酶体途径降解成骨转录因子runx2和蛋白酶体在控制成骨细胞分化中信号分子降解的功能。硼替佐米无法改变依赖β-catenin的记者和规范WNT信号靶基因表达的转录活性。我们还证明了对某些泛素连接酶（E3）的抑制作用上调成骨细胞的分化。

项目成果

Regulation of osteoblastic differentiation by the ubiquitin-proteasome pathway. Interface Oral Health Science 2011

通过泛素-蛋白酶体途径调节成骨细胞分化。

• DOI: 10.1007/978-4-431-54070-0_43
• 发表时间: 2012
• 期刊: Interface Oral Health Science 2011
• 作者: Uyama M;Sato M;Kawanami M;Tamura M
• 通讯作者: Tamura M

Regulation of both osteoblastic and myogenic differentiation by proteoasome inhibitor bortezomib

蛋白酶体抑制剂硼替佐米对成骨细胞和肌源性分化的调节

• 发表时间: 2011
• 作者: Uyama M;Sato M;Kawanami M;Tamura M
• 通讯作者: Tamura M

Wasf2: a novel target of intermittent PTH administration

Wasf2：间歇性 PTH 给药的新靶点

• DOI: 10.3892/ijmm.2013.1315
• 发表时间: 2013
• 期刊: Int J Mol Med
• 影响因子: 5.4
• 作者: Uyama M;Kawanami M;Tamura M;Hisashi Ideno;Uyama M
• 通讯作者: Uyama M

Regulation of osteoblastic differentiation by the proteasome inhibitor bortezomib.

蛋白酶体抑制剂硼替佐米对成骨细胞分化的调节。

• DOI: 10.1111/j.1365-2443.2012.01611.x
• 发表时间: 2012
• 期刊: Genes Cells
• 影响因子: 2.1
• 作者: Uyama M;Sato MM;Kawanami M;Tamura M;Taichi Kamiunten;Uyama M
• 通讯作者: Uyama M

Actions of small molecular inhibitors on anabolic effects of intermittent PTH treatment

小分子抑制剂对间歇性 PTH 治疗合成代谢影响的作用

• 发表时间: 2012
• 作者: Uyama M;Kawanami M;Tamura M
• 通讯作者: Tamura M