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) 的病因是 RUNX2/CBFA1 基因突变，其特征是锁骨和颅骨发育不全。 Runx2/Cbfal是RUNX2/CBFA1的小鼠同源物，该基因的杂合Runx2/Cbfa1基因缺陷小鼠与CCD中的骨异常相似。 CCD经常伴有多生牙、阻生牙和牙齿萌出延迟，但这些原因尚不清楚。为了澄清这些观点，对杂合小鼠的牙齿和牙周组织进行了检查。杂合子小鼠和正常小鼠之间的牙齿数量或牙骨质和牙周膜的形成没有显示出差异。然而，前者牙齿萌出进入口腔的时间明显延迟于后者。前者位于萌出途径的破骨细胞数量明显较低。这些观察结果表明，由于RUNX2/CBFA1单倍体不足而导致的破骨细胞募集受损是CCD中牙齿萌出延迟的原因之一。2）牙齿萌出过程萌出分为萌出途径形成和牙齿垂直移动。我们报道了甲状旁腺激素相关蛋白（PTHrP）和RANKL在前一过程中的贡献和功能。我们还开发了一种新型培养系统，利用萌出的牙齿和牙周组织来测定破骨细胞的形成和激活。3) 由于已知牙周膜 (PDL) 在牙齿萌出过程中发挥重要作用，因此进行了 DNA 微阵列来比较从萌出和未萌出的牙齿中分离出的 PDL 基因表达。有趣的是，CALBINDINi 的表达在大鼠实验性牙齿移动期间在 PDL 的压缩侧表现出高表达，在萌出牙齿的 PDL 中显着高于未萌出牙齿的 PDL。