Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3.
Role of GATA binding protein 4 (GATA4) in the regulation of tooth development via GNAI3.
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GATA 结合蛋白 4 (GATA4) 在通过 GNAI3 调节牙齿发育中的作用
DOI：
10.1038/s41598-017-01689-1
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发表时间：
2017-05-08
影响因子：
4.6
通讯作者：
Ma J
中科院分区：
文献类型：
--
作者：
Guo S;Zhang Y;Zhou T;Wang D;Weng Y;Wang L;Ma J
转录因子GATA 4调节心脏和成骨细胞分化。然而，它在牙齿发育中的作用尚不清楚。因此，我们产生了Wnt 1-Cre; GATA 4
FL/FL
小鼠，牙乳头间充质细胞中GATA 4基因的条件性失活。表型分析显示短根畸形沿着减少表达的牙/成骨标志物。根的顶端区域周围的细胞增殖（但不凋亡）减弱。在体外，我们敲低GATA 4在牙根尖乳头干细胞（SCAPs）的表达。shGATA 4组SCAPs的增殖、迁移和牙/骨分化受到影响。SCAPs中GATA 4的过表达增加了矿化。基于我们先前的iTRAQ结果，鸟嘌呤核苷酸结合蛋白3（GNAI 3）是GATA 4缺失后的独特蛋白之一。G蛋白信号传导参与骨发育、重塑和疾病。在这项研究中，小鼠根部的GATA 4缺失和人SCAPs中的敲低都降低了GNAI 3的表达。双荧光素酶和ChIP测定证实了GATA 4在体外和体内与GNAI 3启动子的直接结合。GNAI 3基因敲低显著降低了SCAPs的牙/成骨分化能力。因此，我们建立的作用GATA 4作为一种新的调节剂的根的发展和阐明其下游的分子事件。
Transcription factor GATA4 regulates cardiac and osteoblast differentiation. However, its role in tooth development is not clear. Therefore, we generated Wnt1-Cre;GATA4
fl/fl
mice, with conditional inactivation of the GATA4 gene in the dental papilla mesenchymal cells. Phenotypic analysis showed short root deformity along with reduced expressions of odonto/osteogenic markers. Proliferation (but not apoptosis) of cells around the apical area of the root was attenuated. In vitro, we knocked down GATA4 expression in stem cells of dental apical papilla (SCAPs). Proliferation, migration and odonto/osteogenic differentiation of SCAPs were affected in the shGATA4 group. Overexpression of GATA4 in SCAPs increased mineralization. Based on our previous iTRAQ results, guanine nucleotide binding proteins 3 (GNAI3) is one of the distinct proteins after GATA4 deletion. G protein signaling is involved in bone development, remodeling, and disease. In this study, both GATA4 deletion in the mouse root and knock-down in human SCAPs decreased the expression of GNAI3. Dual-luciferase and ChIP assay confirmed the direct binding of GATA4 to the GNAI3 promoter, both in vitro and in vivo. GNAI3 knock-down significantly decreased the odonto/osteogenic differentiation ability of SCAPs. We thus establish the role of GATA4 as a novel regulator of root development and elucidate its downstream molecular events.