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骨形态发生蛋白-信号转导分子母抗素信号通路调控小鼠磨牙出生后的冠部牙本质形成

BMP-Smad Signaling Regulates Postnatal Crown Dentinogenesis in Mouse Molar.

作者信息

Omi Maiko, Kulkarni Anshul K, Raichur Anagha, Fox Mason, Uptergrove Amber, Zhang Honghao, Mishina Yuji

机构信息

Department of Biologic and Materials Sciences and Prosthodontics University of Michigan School of Dentistry Ann Arbor MI USA.

出版信息

JBMR Plus. 2019 Nov 14;4(2):e10249. doi: 10.1002/jbm4.10249. eCollection 2020 Feb.

Abstract

Dentinogenesis, a formation of dentin by odontoblasts, is an essential process during tooth development. Bone morphogenetic proteins (BMPs) are one of the most crucial growth factors that contribute to dentin formation. However, it is still unclear how BMP signaling pathways regulate postnatal crown and root dentinogenesis. BMPs transduce signals through canonical Smad and non-Smad signaling pathways including p38 and ERK signaling pathways. To investigate the roles of Smad and non-Smad signaling pathways in dentinogenesis, we conditionally deleted , which encodes the type 1A receptor for BMPs, to remove both Smad and non-Smad pathways in -expressing cells. We also expressed a constitutively activated form of () to increase Smad1/5/9 signaling activity without altered non-Smad activity in odontoblasts. To understand the function of BMP signaling during postnatal dentin formation, Cre activity was induced at the day of birth. Our results showed that loss of BmpR1A in odontoblasts resulted in impaired dentin formation and short molar roots at postnatal day 21. cKO mice displayed a reduction of dentin matrix production compared to controls associated with increased cell proliferation and reduced and expression. In contrast, mutant mice that show increased Smad1/5/9 signaling activity resulted in no overt tooth phenotype. To further dissect the functions of each signaling activity, we generated cKO mice also expressing to restore only Smad1/5/9 signaling activity. Restoring Smad activity in the compound mutant mice rescued impaired crown dentin formation in the cKO mice; however, impaired root dentin formation and short roots were not changed. These results suggest that BMP-Smad signaling in odontoblasts is responsible for crown dentin formation, while non-Smad signaling may play a major role in root dentin formation and elongation. © 2019 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2019 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

摘要

牙本质形成是成牙本质细胞形成牙本质的过程,是牙齿发育过程中的一个重要过程。骨形态发生蛋白(BMPs)是促成牙本质形成的最关键生长因子之一。然而,BMP信号通路如何调节出生后牙冠和牙根的牙本质形成仍不清楚。BMPs通过经典的Smad和非Smad信号通路(包括p38和ERK信号通路)转导信号。为了研究Smad和非Smad信号通路在牙本质形成中的作用,我们有条件地删除了编码BMPs 1A型受体的基因,以去除表达该基因的细胞中的Smad和非Smad通路。我们还在成牙本质细胞中表达了一种组成型激活形式的(),以增加Smad1/5/9信号活性,而不改变非Smad活性。为了了解出生后牙本质形成过程中BMP信号的功能,在出生当天诱导Cre活性。我们的结果表明,成牙本质细胞中BmpR1A的缺失导致出生后第21天牙本质形成受损和磨牙根缩短。与对照组相比,cKO小鼠的牙本质基质产生减少,这与细胞增殖增加以及和表达减少有关。相反,显示Smad1/5/9信号活性增加的突变小鼠没有明显的牙齿表型。为了进一步剖析每种信号活性的功能,我们还生成了同时表达的cKO小鼠,以仅恢复Smad1/5/9信号活性。在复合突变小鼠中恢复Smad活性挽救了cKO小鼠中受损的牙冠牙本质形成;然而,受损的牙根牙本质形成和短根并没有改变。这些结果表明,成牙本质细胞中的BMP-Smad信号负责牙冠牙本质形成,而非Smad信号可能在牙根牙本质形成和伸长中起主要作用。©2019作者。由Wiley Periodicals, Inc.代表美国骨与矿物质研究学会出版。©2019作者。由Wiley Periodicals, Inc.代表美国骨与矿物质研究学会出版。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32f7/7017888/83659ca30add/JBM4-4-e10249-g001.jpg

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