Klf5 Mediates Odontoblastic Differentiation through Regulating Dentin-Specific Extracellular Matrix Gene Expression during Mouse Tooth Development.
Klf5 Mediates Odontoblastic Differentiation through Regulating Dentin-Specific Extracellular Matrix Gene Expression during Mouse Tooth Development.
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Klf5 通过调节小鼠牙齿发育过程中牙本质特异性细胞外基质基因表达来介导成牙本质细胞分化
DOI：
10.1038/srep46746
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发表时间：
2017-04-25
影响因子：
4.6
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Chen Z;Zhang Q;Wang H;Li W;Wang F;Wan C;Deng S;Chen H;Yin Y;Li X;Xie Z;Chen S
Klf5是Krüppel样转录因子家族的成员，在胚胎发育、细胞增殖、分化、迁移和凋亡过程中发挥重要作用。本研究旨在探讨Klf 5在成牙本质细胞分化过程中的分子机制。Klf 5、成牙本质细胞分化标志物Dspp和Dmp 1在小鼠牙齿发育不同阶段的成牙本质细胞和小鼠牙乳头间充质细胞中共定位表达。Klf5能够促进小鼠牙乳头间充质细胞向成牙本质细胞分化并促进其矿化。Klf5过表达可上调小鼠牙乳头间充质细胞Dspp和Dmp 1基因的表达。计算机模拟分析发现，在Dmp1和Dspp基因的启动子和第一内含子中存在几个假定的Klf5结合位点，这些位点在物种品系之间是同源的。电泳迁移率变动分析和染色质免疫沉淀分析表明，Klf5结合这些图案在体外和完整的细胞。Dmp 1基因的作用区域位于启动子区，Klf 5基因对Dspp活性的作用区域位于Dspp基因的第一内含子。我们的研究结果表明Klf5通过不同的机制激活Dmp 1和Dspp基因转录，并证明Klf5在成牙本质细胞分化中起着关键作用。
Klf5, a member of the Krüppel-like transcription factor family, has essential roles during embryonic development, cell proliferation, differentiation, migration and apoptosis. This study was to define molecular mechanism of Klf5 during the odontoblastic differentiation. The expression of Klf5, odontoblast-differentiation markers, Dspp and Dmp1 was co-localized in odontoblastic cells at different stages of mouse tooth development and mouse dental papilla mesenchymal cells. Klf5 was able to promote odontoblastic differentiation and enhance mineral formation of mouse dental papilla mesenchymal cells. Furthermore, overexpression of Klf5 could up-regulate Dspp and Dmp1 gene expressions in mouse dental papilla mesenchymal cells. In silico analysis identified that several putative Klf5 binding sites in the promoter and first intron of Dmp1 and Dspp genes that are homologous across species lines. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis indicated that Klf5 bound to these motifs in vitro and in intact cells. The responsible regions of Dmp1 gene were located in the promoter region while effect of Klf5 on Dspp activity was in the first intron of Dspp gene. Our results identify Klf5 as an activator of Dmp1 and Dspp gene transcriptions by different mechanisms and demonstrate that Klf5 plays a pivotal role in odontoblast differentiation.