Bone regenerative medicine by introducing ets family of gene

Ets癌基因家族在胚胎发生、分化、细胞生长和细胞凋亡等基本生物学事件中起重要作用。此前，我们发现Ets家族中的一个E1AF能激活基质金属蛋白酶(MMPs)的表达，而MMPs与骨生成有关。本研究的目的是探讨Ets基因对成骨细胞的诱导分化作用。我们构建了E1AF表达载体，并通过荧光素酶活性检测了骨桥蛋白基因表达的激活情况。由于在稳定表达E1AF的细胞中未检测到E1AF蛋白的表达，而E1AF的mRNA表达良好，因此E1AF在转录后水平上受到调控。我们发现E1AF是通过泛素-蛋白酶体途径降解的。我们检测了抑制骨生成的腺病毒E1a对E1AF介导的基因表达激活的影响。结果表明，E1a抑制了E1AF靶向基因的转录，提示E1AF与骨生成有关。

Ets oncogene family plays an important role for basic biological events such as embryogenesis, differentiation, cell growth and apoptosis. Previously, we found that one of the ets family, E1AF, activates the expression of matrixmetalloproteases (MMPs), which is related to bone production. The objective of this research is to examine whether ets genes induce the differentiation of osteoblast.We produced an E1AF expression vector and examined the activation of osteopontin gene expression by luciferase assay. The expression was activated by E1AF in dose-dependent manner.Since E1AF protein failed to be detected in the cells expressing E1AF stably, whereas the mRNA was expressed well, E1AF is regulated in post-transcriptional level. We found that E1AF is degraded by ubiquitin-proteasome pathway.We examined the effect of adenovirus E1A, which inhibits bone production, on the activation of gene expression mediated by E1AF. The data showed that E1A inhibited the transcription from the gene targeted by E1AF.These findings indicate that E1AF has some relation with bone production.