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The induction of periodontal tissues by dentin-derived matrix

牙本质基质诱导牙周组织

基本信息

批准号：
14370577
负责人：
TAKANO Yoshiro
金额：
$ 7.55万
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 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370577/
关键词：
dentin cementum regeneration periodontal ligament non-collagenous dentin matrix bisphosphonates HEBP tooth DSP bisphosphonate

项目摘要

The demineralized dentin matrix has been known to have a high potential to induce ectopic bone formation at the site of implantation, implicating presence of certain bioactive molecules in the dentin matrix that facilitate differentiation of local cells into the chondrogenic and/or osteogenic cells. The aim of current investigation was to test a hypothesis that matrix components of the forming root dentin may in fact contribute to the induction of periodontal tissues, primarily on the differentiation of periodontal mesenchymal cells to cementoblasts, in the process of tooth development. The final goal of the study was to identify the bioactive molecule(s) and apply the data for the regeneration of periodontal tissues.HEBP is a type of bisphosphonate known to have high inhibitory effects on biological mineralization without causing notable interferences on the matrix forming functions of the cells of bones and teeth. We have noticed that, in the HEBP-affected animals, thick cellular cem … More entum is deposited on the root surface, where only acellular cernentum is known to form under physiological conditions, if mineralization of the forming root dentin is inhibited and hence the non-mineralized dentin surface is exposed to the future periodontal ligament. Immunohistochemical date revealed that dentin sialaprotein, one of major non-collagenous components of dentin matrix, penetrates through the non-mineralized layers of dentin and diffuses into the future periodontal ligament, implicating dynamic translocation of the proteinaceous molecules through dentin layers, if mineralization of dentin is inhibited. In such areas, amelogenin proteins could not be localized by immunohistochemistry, despite the fact that dentin matrix contains low molecular amelogenins and that odontoblasts are reported to transiently express amelogenin messages at least by PCR analyses.In normal tooth development, the epithelial-mesenchymal interface between the enamel and dentin forming cell layers is the site of crosstalk, where various signaling molecules are crisscrossing. Our data indicate that non-mineralized mantle dentin layers allow almost free passage of various molecules between the two cell layers that respectively generate non-collagenous dentin matrix proteins and certain amelogenin mRNA splice products, which might contribute to the induction of cementoblasts and further the formation of periodontal tissues. Introduction of highly sensitive analytical methods in future studies may allow visualization of distinct localization of candidate molecules for the induction of cementoblasts at the site of de novo formation of root dentin surface. Less

已知脱矿质牙本质基质极有可能在植入部位诱导异位骨形成，这表明牙本质基质中存在某些生物活性分子，促进局部细胞分化成软骨细胞和/或成骨细胞。当前研究的目的是检验一个假设，即形成的牙根牙本质的基质成分实际上可能有助于牙周组织的诱导，主要是在牙齿发育过程中牙周间充质细胞向成牙骨质细胞的分化。该研究的最终目标是鉴定生物活性分子并将数据应用于牙周组织的再生。HEBP 是一种双膦酸盐，已知对生物矿化具有高度抑制作用，但不会对骨骼和牙齿细胞的基质形成功能造成显着干扰。我们注意到，在受 HEBP 影响的动物中，厚厚的细胞牙本质沉积在牙根表面，如果形成的根牙本质的矿化受到抑制，则在生理条件下只有无细胞牙本质形成，因此未矿化的牙本质表面暴露于未来的牙周膜。免疫组织化学数据显示，牙本质唾液蛋白（牙本质基质的主要非胶原成分之一）穿透牙本质的非矿化层并扩散到未来的牙周膜中，这意味着如果牙本质的矿化受到抑制，则表明蛋白质分子会通过牙本质层动态易位。在这些区域中，牙本质蛋白不能通过免疫组织化学定位，尽管事实上牙本质基质含有低分子牙釉蛋白，并且据报道至少通过PCR分析成牙本质细胞瞬时表达牙釉蛋白信息。在正常牙齿发育中，牙釉质和牙本质形成细胞层之间的上皮-间质界面是串扰的位点，其中各种信号传导分子是交叉的。我们的数据表明，非矿化的地幔牙本质层允许各种分子在两个细胞层之间几乎自由通过，分别产生非胶原牙本质基质蛋白和某些牙釉蛋白mRNA剪接产物，这可能有助于诱导成牙骨质细胞并进一步形成牙周组织。在未来的研究中引入高度敏感的分析方法可能会允许在牙根牙本质表面从头形成部位诱导成牙骨质细胞的候选分子的不同定位的可视化。较少的