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Basic research to clarify the mechanism of delayed tooth eruption in cleidocranial dysplasia

阐明锁骨颅骨发育不良导致牙齿萌出延迟机制的基础研究

基本信息

批准号：
14370690
负责人：
SUDA Naoto
金额：
$ 7.74万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370690/
关键词：
tooth eruption cleidocranial dysplasia Runx2 runx2

项目摘要

1) The cause of the Cleidocranial dysplasia (CCD), characterized by hypoplastic clavicle and cranial bones, is known as a gene mutation of RUNX2/CBFA1. Runx2/Cbfal is a mouse homolog of RUNX2/CBFA1 and heterozygous Runx2/Cbfa1 gene-deficient mice of this gene resembles to the bone abnormalities in CCD. CCD frequently accompanies supernumerary teeth and impaction and delayed eruption of teeth, however, these causes are yet not known. To clarify these points, teeth and periodontal tissues were examined in heterozygous mice. The number of teeth or the formation of cementum and periodontal ligament did not show difference between heterozygous and normal mice. However, the timing of tooth eruption into the oral cavity was significantly delayed in the former than in the latter. The osteoclast number located in the eruption pathway was significantly lower in the former., These observations suggest that impaired osteoclast recruitment due to the haploinsufficiency of RUNX2/CBFA1 as one of the cause of the delayed tooth eruption in CCD.2) The process of tooth eruption is divided into the eruption 'pathway formation and vertical tooth movement. We reported the contribution and function of parathyroid hormone-related protein (PTHrP) and RANKL in the former process. We also developed a novel culture system to assay the osteoclast formation and activation using the erupting teeth and periodontal tissues.3) Since the periodontal ligament (PDL) is known to play an important role during the tooth eruption, DNA microarray was carried out to compare the gene expression of PDL isolated from erupting and non-erupting teeth. Interestingly, the expression of CALBINDINi, which is also known to show high expression in the compression side of the PDL during the experimental tooth movement in rats, was dramatically higher in PDLs from erupting teeth than non-erupting teeth.

1)锁骨颅骨发育不良（CCD）的原因是锁骨和颅骨发育不全，被称为RUNX 2/CBFA 1基因突变。Runx 2/Cbfal是RUNX 2/CBFA 1的小鼠同源物，并且该基因的杂合Runx 2/Cbfa 1基因缺陷小鼠类似于CCD中的骨异常。CCD常伴有多生牙、阻生牙和延迟萌出牙，然而，这些原因尚不清楚。为了阐明这些观点，在杂合子小鼠中检查了牙齿和牙周组织。杂合子小鼠与正常小鼠的牙齿数、牙骨质和牙周膜的形成无明显差异。然而，牙齿萌出进入口腔的时间在前者比后者明显延迟。位于萌出路径的破骨细胞数量在前者中明显较低，提示RUNX 2/CBFA 1单倍型不足导致破骨细胞募集障碍是导致牙齿萌出延迟的原因之一。2）牙齿萌出过程分为萌出通道形成和牙齿垂直移动两个阶段。我们报道了甲状旁腺相关蛋白（PTHrP）和RANKL在前一过程中的作用和贡献。我们还开发了一种新的培养系统，用于检测破骨细胞的形成和激活。3）由于牙周膜（PDL）在牙齿萌出过程中起着重要作用，我们利用DNA微阵列技术比较了萌出牙和非萌出牙PDL的基因表达。有趣的是，在大鼠实验性牙齿移动过程中，CALBINDINI在PDL的压缩侧也显示出高表达，其在萌出牙齿的PDL中的表达显著高于非萌出牙齿。