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成骨细胞特异性转录因子在牙根形成中的位点特异性功能及调控

Site-specific function and regulation of Osterix in tooth root formation.

作者信息

He Y D, Sui B D, Li M, Huang J, Chen S, Wu L A

机构信息

Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China.

State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, China.

出版信息

Int Endod J. 2016 Dec;49(12):1124-1131. doi: 10.1111/iej.12585. Epub 2016 Jan 4.

DOI:10.1111/iej.12585
PMID:26599722
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5005108/
Abstract

Congenital diseases of tooth roots, in terms of developmental abnormalities of short and thin root phenotypes, can lead to loss of teeth. A more complete understanding of the genetic molecular pathways and biological processes controlling tooth root formation is required. Recent studies have revealed that Osterix (Osx), a key mesenchymal transcriptional factor participating in both the processes of osteogenesis and odontogenesis, plays a vital role underlying the mechanisms of developmental differences between root and crown. During tooth development, Osx expression has been identified from late embryonic to postnatal stages when the tooth root develops, particularly in odontoblasts and cementoblasts to promote their differentiation and mineralization. Furthermore, the site-specific function of Osx in tooth root formation has been confirmed, because odontoblastic Osx-conditional knockout mice demonstrate primarily short and thin root phenotypes with no apparent abnormalities in the crown (Journal of Bone and Mineral Research 30, 2014 and 742, Journal of Dental Research 94, 2015 and 430). These findings suggest that Osx functions to promote odontoblast and cementoblast differentiation and root elongation only in root, but not in crown formation. Mechanistic research shows regulatory networks of Osx expression, which can be controlled through manipulating the epithelial BMP signalling, mesenchymal Runx2 expression and cellular phosphorylation levels, indicating feasible routes of promoting Osx expression postnatally (Journal of Cellular Biochemistry 114, 2013 and 975). In this regard, a promising approach might be available to regenerate the congenitally diseased root and that regenerative therapy would be the best choice for patients with developmental tooth diseases.

摘要

牙根先天性疾病,就短而细的牙根表型发育异常而言,可导致牙齿脱落。需要更全面地了解控制牙根形成的遗传分子途径和生物学过程。最近的研究表明,骨形成蛋白受体激活因子2(Osx)是一种参与成骨和牙发生过程的关键间充质转录因子,在牙根和牙冠发育差异机制中起着至关重要的作用。在牙齿发育过程中,从胚胎后期到出生后牙根发育阶段都已检测到Osx的表达,特别是在成牙本质细胞和成牙骨质细胞中,以促进它们的分化和矿化。此外,Osx在牙根形成中的位点特异性功能已得到证实,因为成牙本质细胞Osx条件性敲除小鼠主要表现出短而细的牙根表型,而牙冠无明显异常(《骨与矿物质研究杂志》第30卷,2014年,第742页;《牙科研究杂志》第94卷,2015年,第430页)。这些发现表明,Osx仅在牙根中发挥促进成牙本质细胞和成牙骨质细胞分化以及牙根伸长的作用,而在牙冠形成中则不然。机制研究表明了Osx表达的调控网络,该网络可通过操纵上皮骨形态发生蛋白(BMP)信号、间充质Runx2表达和细胞磷酸化水平来控制,这表明了出生后促进Osx表达的可行途径(《细胞生物化学杂志》第114卷,2013年,第975页)。在这方面,可能有一种有前景的方法可用于再生先天性病变的牙根,并且再生疗法将是发育性牙齿疾病患者的最佳选择。

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Osterix controls cementoblast differentiation through downregulation of Wnt-signaling via enhancing DKK1 expression.骨形成蛋白2通过增强DKK1表达下调Wnt信号通路来调控成牙骨质细胞分化。
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Osterix regulates tooth root formation in a site-specific manner.
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