Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China.
Int J Oral Sci. 2022 Apr 14;14(1):20. doi: 10.1038/s41368-022-00172-6.
Multiple signaling pathways are involved in the regulation of cell proliferation and differentiation in odontogenesis and dental tissue renewal, but the details of these mechanisms remain unknown. Here, we investigated the expression patterns of a transcription factor, Krüppel-like factor 6 (KLF6), during the development of murine tooth germ and its function in odontoblastic differentiation. KLF6 was almost ubiquitously expressed in odontoblasts at various stages, and it was co-expressed with P21 (to varying degrees) in mouse dental germ. To determine the function of Klf6, overexpression and knockdown experiments were performed in a mouse dental papilla cell line (iMDP-3). Klf6 functioned as a promoter of odontoblastic differentiation and inhibited the proliferation and cell cycle progression of iMDP-3 through p21 upregulation. Dual-luciferase reporter assay and chromatin immunoprecipitation showed that Klf6 directly activates p21 transcription. Additionally, the in vivo study showed that KLF6 and P21 were also co-expressed in odontoblasts around the reparative dentin. In conclusion, Klf6 regulates the transcriptional activity of p21, thus promoting the cell proliferation to odontoblastic differentiation transition in vitro. This study provides a theoretical basis for odontoblast differentiation and the formation of reparative dentine regeneration.
多种信号通路参与牙发生和牙组织更新过程中细胞增殖和分化的调节，但这些机制的细节尚不清楚。在这里，我们研究了转录因子 Krüppel 样因子 6（KLF6）在鼠牙胚发育过程中的表达模式及其在成牙本质细胞分化中的功能。KLF6 在不同阶段的成牙本质细胞中几乎广泛表达，并与 P21（不同程度）在小鼠牙胚中共同表达。为了确定 Klf6 的功能，在鼠牙乳头细胞系（iMDP-3）中进行了过表达和敲低实验。Klf6 作为成牙本质细胞分化的启动子，通过上调 p21 抑制 iMDP-3 的增殖和细胞周期进程。双荧光素酶报告基因检测和染色质免疫沉淀实验表明，Klf6 可直接激活 p21 转录。此外，体内研究表明，KLF6 和 P21 在修复性牙本质周围的成牙本质细胞中也有共表达。总之，Klf6 调节 p21 的转录活性，从而促进体外细胞增殖向成牙本质细胞分化的转变。本研究为成牙本质细胞分化和修复性牙本质再生提供了理论基础。
