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Molecular pathological study of tooth germ and odonto genic tumor

牙胚及牙源性肿瘤的分子病理学研究

基本信息

批准号：
12470385
负责人：
NAGAI Noriyuki
金额：
$ 8.7万
依托单位：
OKAYAMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470385/
关键词：
Tooth Germ BMP Cbfa1 Odontogenic Tumor Basement Membrane Type IV Collagen 成長因子 Cbfal

项目摘要

To clarify the reciprocal roles of epithelium and mesenchyme in tooth germ differentiation process, we investigated the localization and change of BMP family gene expression and each alpha chain of collagen IV, which is a main basal membrane component, in tooth germ development. The expressions of BMP-4 and BMP-7 at fetal age 11^<th> day and BMP-2 expression at fetal age 12^<th> day were shown. Moreover, each of alpha chains of collagen IV was localized in basal membrane of tooth germ epithelium in a stage dependent manner.We examined the role of BMP family to understand the odontogenic tumor cell differentiation. In ameloblastoma, amelogenin expression was detected in tumor cells with a morphologic similarity to early tooth germ. In terms of functional differentiation, amelogenin was expressed in late differentiation stage. In desmoplastic ameloblastoma, BMP family was shown to have a possible role for the differentiation of stroma into periodontal tissue. In adenomatoid odontogenic tumor, BMP family localization was resembled to matrix formation stage of tooth germ. In summary, we showed the special role of BMP family in induction and differentiation of each tissue type into parenchyma and stroma in odontogenic tumors.Then we analyzed the role of cbfal in matrix protein expression and bone formation in mouse tooth germ and showed its role in matrix protein expression and morphologic formation of tooth germ. Furthermore, cbaf1 knock-out mouse studies demonstrated that differentiation and transcription regulation in incisor tooth germ by cbfa was different than in osteoblasts.

为了阐明上皮和间质在牙胚分化过程中的相互作用，我们研究了BMP家族基因表达和主要基底膜成分IV型胶原α链在牙胚发育中的定位和变化。BMP-4、BMP-7在胎龄11d时表达，BMP-2在胎龄12d时表达。此外，IV型胶原蛋白的每一条α链都以阶段依赖的方式定位于牙胚上皮基底膜。我们研究了BMP家族在了解牙源性肿瘤细胞分化中的作用。在成釉细胞瘤中，在形态上与早期牙胚相似的肿瘤细胞中检测到釉原蛋白的表达。在功能分化方面，釉原蛋白在分化后期有表达。在促结缔组织增生性成釉细胞瘤中，BMP家族可能在基质向牙周组织分化中起作用。在腺瘤样牙源性肿瘤中，BMP家族定位类似于牙胚基质形成阶段。综上所述，我们展示了BMP家族在牙源性肿瘤中每种组织类型诱导和分化为实质和基质中的特殊作用。然后，我们分析了cbfal在小鼠牙胚中基质蛋白表达和骨形成中的作用，并揭示了其在基质蛋白表达和牙胚形态形成中的作用。此外，cbaf1基因敲除小鼠的研究表明，cbaf1基因在切牙胚中的分化和转录调控不同于成骨细胞。