Regulation of osteoblastic differentiation by the ubiquitin-proteasome pathway. Interface Oral Health Science 2011
Regulation of osteoblastic differentiation by the ubiquitin-proteasome pathway. Interface Oral Health Science 2011
复制标题
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
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Tamura M
中科院分区：
文献类型：
--
作者：
Uyama M;Sato M;Kawanami M;Tamura M
在真核细胞中，大多数细胞内蛋白质的降解是通过泛素-蛋白酶体途径进行的。该途径是多种疾病的治疗靶点。最近的观察表明，骨代谢是由泛素-蛋白酶体途径调节的，并且蛋白酶体活性对于成骨转录因子的激活是至关重要的。硼替佐米是一种26 S蛋白酶体抑制剂，用作治疗多发性骨髓瘤的抗癌药物，其临床疗效与骨标志物的增加有关。此外，已报道硼替佐米在体外和体内诱导成骨细胞分化。根据我们的研究，硼替佐米不仅诱导成骨细胞分化，而且抑制培养的多能C2 C12细胞的肌源性分化。
In eukaryotic cells, degradation of most intracellular proteins is carried out by the ubiquitin–proteasome pathway. This pathway is the therapeutic target in several diseases. Recent observations suggest that bone metabolism is regulated by the ubiquitin–proteasome pathway, and that proteasome activity is critical for activation of osteogenic transcription factors. The clinical efficacy of bortezomib, a 26S proteasome inhibitor used as an anticancer drug in the treatment of multiple myeloma, has been linked to an increase in bone markers. Also, bortezomib has been reported to induce differentiation of osteoblasts both in vitro and in vivo. From our studies, bortezomib not only induces osteoblastic differentiation but also inhibits myogenic differentiation in pluripotent C2C12 cells in culture.