Zinc balance is critical for NFI-C mediated regulation of odontoblast differentiation
Zinc balance is critical for NFI-C mediated regulation of odontoblast differentiation
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DOI：
10.1002/jcb.23421
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发表时间：
2012-03-01
影响因子：
4
通讯作者：
Park, Joo-Cheol
中科院分区：
文献类型：
--
作者：
Oh, Hyun-Jung;Lee, Hye-Kyung;Park, Joo-Cheol
锌是生长、发育和维持的多种代谢和细胞信号传导途径所必需的微量元素。缺锌与骨畸形和口腔疾病有关。锌转运蛋白Zip 13缺陷的小鼠表现出结缔组织和骨骼疾病、异常的门牙和臼齿中的牙根牙本质形成减少，并且与核因子I-C（NFI-C）缺陷的小鼠具有形态学相似的表型。然而，锌在NFI-C信号介导的成牙本质细胞分化和牙本质形成中的确切功能尚不清楚。在这里，我们表明，锌刺激金属转录因子-1的表达，但减少NFI-C在成牙本质细胞MDPC-23细胞的表达。锌还增强Smad 2/3（p-Smad 2/3）的磷酸化，并增加NFI-C和p-Smad 2/3在胞浆中的结合效率。相反，缺锌导致NFI-C在细胞核中积累。因此，NFI-C具有转录因子的生物学特性，包括对金属硫蛋白-1和牙本质唾液磷蛋白（DSPP）启动子的DNA结合亲和力，以及DSPP基因的转录激活。缺锌促进成牙本质细胞DSPP表达和牙本质矿化，而锌充足则降低DSPP表达，牙本质矿化稍延迟。这些数据表明，锌的平衡需要通过核积累和NFI-C的调节成牙本质细胞分化和牙本质形成在牙本质发生。J.细胞。生物化学113：877887，2012年。(C)2011 Wiley Periodicals，Inc.
Zinc is trace element essential for diverse metabolic and cellular signaling pathways for the growth, development, and maintenance. Zinc deficiency is involved in bone malformations and oral disease. Mice deficient in zinc transporter Zip13 show connective tissue and skeletal disorders, abnormal incisor teeth, and reduced root dentin formation in the molar teeth and share a morphologically similar phenotype to nuclear factor I-C (NFI-C)-deficient mice. However, the precise function of zinc in NFI-C signaling-mediated odontoblast differentiation and dentin formation remains unclear. Here, we show that zinc stimulated the expression of metal transcription factor-1, but decreased NFI-C expression in odontoblastic MDPC-23 cells. Zinc also enhanced the phosphorylation of Smad2/3 (p-Smad2/3) and increased the binding efficiency of NFI-C and p-Smad2/3 in the cytoplasm. In contrast, zinc deficiency resulted in the accumulation of NFI-C into nucleus. Consequently, NFI-C had the biologic properties of a transcription factor, including DNA binding affinity for metallothionein-1 and the dentin sialophosphoprotein (DSPP) promoter, and transcriptional activation of the DSPP gene. Furthermore, zinc deficiency condition promoted DSPP expression in odontoblasts and dentin mineralization, while zinc sufficiency condition decreased DSPP expression and slightly delayed dentin mineralization. These data suggest that zinc equilibrium is required for odontoblast differentiation and dentin formation during dentinogenesis through the nuclear accumulation and modulation of NFI-C. J. Cell. Biochem. 113: 877887, 2012. (C) 2011 Wiley Periodicals, Inc.