Trps1 transcription factor regulates mineralization of dental tissues and proliferation of tooth organ cells
Trps1 transcription factor regulates mineralization of dental tissues and proliferation of tooth organ cells
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DOI：
10.1016/j.ymgme.2019.01.014
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发表时间：
2019-04-01
影响因子：
3.8
通讯作者：
Napierala, Dobrawa
中科院分区：
文献类型：
--
作者：
Goss, Morgan;Socorro, Mairobys;Napierala, Dobrawa
TRPS 1基因的突变导致毛发鼻指综合征（TRPS），一种伴有牙齿异常的骨骼发育不良。TRPS牙齿表型表明TRPS 1调节牙齿发生的多个方面，包括牙齿数量和大小。以前的研究描绘的Trps 1表达在整个胚胎牙齿发育的小鼠检测到强烈的Trps 1表达在牙齿间充质细胞，preodontoblasts，和牙囊，表明TRPS牙齿表型的结果在早期发育过程中的异常。在这项研究中，分析了Trps 1（+/-）和Trps 1（-/-）小鼠，以确定Trps 1缺陷对牙发生的后果。我们的重点是牙齿形成的方面，在TRPS和潜在的分子异常TRPS牙齿表型的干扰。臼齿的微型计算机断层扫描分析用于确定牙齿大小，牙冠形状和牙组织的矿化。这些分析揭示了一个Trps 1等位基因的破坏足以损害雄性和雌性小鼠的牙本质矿化。釉质矿物质密度下降，只有在男性，而矿化的根牙组织减少，只有在女性。此外，在Trps 1（+/-）雌性中检测到明显较小的牙齿。牙齿器官的组织形态学分析显示Trps 1（-/-）小鼠的前后径减少。BrdU掺入法检测Trps 1（-/-）牙器官中间充质细胞和上皮细胞的增殖减少。Runx 2和Osx成骨转录因子的免疫组织化学揭示了它们在Trps 1（-/-）牙齿器官中空间分布的变化，并揭示了Trps 1对Osx表达的细胞类型特异性要求。总之，这项研究表明，Trps 1是一个积极的调节细胞增殖的牙齿间充质和上皮细胞，这表明，microdontia在TRPS可能是由于减少细胞增殖发育中的牙齿器官。此外，在Trps 1（+/-）小鼠中观察到的矿化减少可能为TRPS患者报告的广泛龋齿提供了一些解释。
Mutations of the TRPS1 gene cause trichorhinophalangeal syndrome (TRPS), a skeletal dysplasia with dental abnormalities. TRPS dental phenotypes suggest that TRPS1 regulates multiple aspects of odontogenesis, including the tooth number and size. Previous studies delineating Trps1 expression throughout embryonic tooth development in mice detected strong Trps1 expression in dental mesenchyme, preodontoblasts, and dental follicles, suggesting that TRPS dental phenotypes result from abnormalities in early developmental processes. In this study, Trps1(+/-) and Trps1(-/-) mice were analyzed to determine consequences of Trps1 deficiency on odontogenesis. We focused on the aspects of tooth formation that are disturbed in TRPS and on potential molecular abnormalities underlying TRPS dental phenotypes. Microcomputed tomography analyses of molars were used to determine tooth size, crown shape, and mineralization of dental tissues. These analyses uncovered that disruption of one Trps1 allele is sufficient to impair mineralization of dentin in both male and female mice. Enamel mineral density was decreased only in males, while mineralization of the root dental tissues was decreased only in females. In addition, significantly smaller teeth were detected in Trps1(+/-) females. Histomorphometric analyses of tooth organs showed reduced anterior-posterior diameter in Trps1(-/-) mice. BrdU-incorporation assay detected reduced proliferation of mesenchymal and epithelial cells in Trps1(-/-) tooth organs. Immunohistochemistry for Runx2 and Osx osteogenic transcription factors revealed changes in their spatial distribution in Trps1(-/-) tooth organs and uncovered cell-type specific requirements of Trps1 for Osx expression. In conclusion, this study has demonstrated that Trps1 is a positive regulator of cell proliferation in both dental mesenchyme and epithelium, suggesting that the microdontia in TRPS is likely due to decreased cell proliferation in developing tooth organs. Furthermore, the reduced mineralization observed in Trps1(+/-) mice may provide some explanation for the extensive dental caries reported in TRPS patients.