Resolution of the wound healing mechanism of dertin-pulp complex and application of the knowledge on it to regenerative medicine

本课题以牙本质再生治疗及其技术的发展为目标，进行了多方面的实验研究，取得了以下结果：体外实验表明，海藻酸凝胶可作为牙本质再生的支架材料，神经营养因子可影响牙髓细胞的分化和矿化，腱生蛋白抑制牙髓细胞中的细胞粘附，并且通过由生长因子调节的腱生蛋白表达的变化来调节细胞粘附，当将BMP-2添加到牙髓细胞上时，DSPP mRNA的表达变强并且基质的量增加，并且PDGF参与牙髓组织的伤口愈合过程中的牙本质形成等。另一方面，在体内实验中，结果表明，磷酸化胶原复合物是BMP-2的有效载体，CCl 2激光与粘合剂复合树脂联合应用直接盖髓是有效的，牙髓组织中含有具有硬组织形成活性的物质和细胞，磷酸钙骨水泥具有良好的生物相容性，可用作盖髓材料，在牙髓细胞的创伤愈合过程中rFIP-2B mRNA表达增加，并且该基因的启动子被创伤刺激激活，牙髓干细胞导入方法在牙本质再生中有效，当牙髓组织的创伤部分的环境最佳时，EMD促进牙本质再生，金属硫蛋白参与牙髓组织创洞后伤口愈合过程中牙髓细胞的增殖和分化，以及细胞死亡控制在牙髓组织伤口愈合过程中的重要性等，本课题结束后，将继续开展指导牙本质有效再生的技术开发实验。

In this subject, aiming at development of dentin regeneration therapy and its technology, various experiments were conducted, and the following results were obtained.In vitro experiments, it became clear that alginic acid gel is useful as scaffold for dentin regeneration, that neurotrophic factor affects differentiation and mineralization of a pulp cells, that tenascin inhibits cell adhesion in pulp cells and cell adhesion is adjusted through the change of tenascin expression regulated by the growth factor, that expression of DSPP mRNA becomes strong and the amount of matrix increases when BMP-2 is added onto the pulp cells, and that PDGF participates in dentin formation in the wound healing process of pulp tissue, etc. On the other hand, in vivo experiments, it became clear that phosphophorynlcollagen complex serves as effective carrier of BMP-2, that the combined use of CCl2 laser and adhesive composite resin in direct pulp capping is effective, that pulp tissue contains the substance and cell which have hard tissue formation activity, that calcium phosphate cement are excellent in biocompatibility and it can be applied as pulp capping material, that rFIP-2B mRNA expression increases in the wound healing process in pulp cells and the promoter of this gene is activated by wound stimulus, that pulp stem cell introducing method is effective in dentin regeneration, that EMD promotes dentin regeneration when the environment of wound part of pulp tissue is optimum, that metallothionein participates in proliferation and differentiation of pulp cells in wound healing of pulp tissue after cavity preparation, and that cell death control is very important in wound healing process of pulp tissue, etc.Further experiments for developing technology which guides effective regeneration of dentin is to be continued after this research subject is over.