Runx3 negatively regulates Osterix expression in dental pulp cells.
Runx3 negatively regulates Osterix expression in dental pulp cells.
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DOI：
10.1042/bj20070104
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发表时间：
2007-07
期刊：
影响因子：
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通讯作者：
Li Zheng;K. Iohara;M. Ishikawa;T. Into;T. Takano-Yamamoto;K. Matsushita;M. Nakashima
中科院分区：
文献类型：
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作者：
Li Zheng;K. Iohara;M. Ishikawa;T. Into;T. Takano-Yamamoto;K. Matsushita;M. Nakashima
Osterix是一种含锌指的转录因子，是成骨细胞分化和骨形成所必需的。Osterix也在牙胚的牙间充质细胞中表达。然而，Osterix在牙齿发育中的转录调控尚不清楚。骨生成的遗传研究将Osterix置于Runx 2的下游（Runt相关2）。Osterix在成牙本质细胞中的表达在体内终末分化过程中与Runx 3重叠。Runx 3下调小鼠DPC（牙髓细胞）中的Osterix表达。因此，研究Runx 3对牙齿发育中Osterix表达的调节作用。Runx 3的强制表达下调了人胚肾293细胞系中Osterix启动子的活性。当Osterix启动子上的Runx 3响应元件（相对于帽位点位于-713至-707 bp（位点3，AGTGGTT））突变时，这种下调被废除。此外，电泳迁移率变动分析和染色质免疫沉淀分析在小鼠DPC证明Runx 3的Osterix启动子的直接功能结合。这些结果表明，在牙齿发育过程中，在牙髓细胞分化成牙本质细胞的过程中，Runx 3对Osterix表达的转录调控。
Osterix, a zinc-finger-containing transcription factor, is required for osteoblast differentiation and bone formation. Osterix is also expressed in dental mesenchymal cells of the tooth germ. However, transcriptional regulation by Osterix in tooth development is not clear. Genetic studies in osteogenesis place Osterix downstream of Runx2 (Runt-related 2). The expression of Osterix in odontoblasts overlaps with Runx3 during terminal differentiation in vivo. Runx3 down-regulates Osterix expression in mouse DPCs (dental pulp cells). Therefore the regulatory role of Runx3 on Osterix expression in tooth development was investigated. Enforced expression of Runx3 down-regulated the activity of the Osterix promoter in the human embryonic kidney 293 cell line. When the Runx3 responsive element on the Osterix promoter, located at -713 to -707 bp (site 3, AGTGGTT) relative to the cap site, was mutated, this down-regulation was abrogated. Furthermore, electrophoretic mobility-shift assay and chromatin immunoprecipitation assays in mouse DPCs demonstrated direct functional binding of Runx3 to the Osterix promoter. These results demonstrate the transcriptional regulation of Osterix expression by Runx3 during differentiation of dental pulp cells into odontoblasts during tooth development.