| Project/Area Number |
14370577
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TAKANO Yoshiro Tokyo Medical and Dental University, Biostructural Science, Professor, 大学院・医歯学総合研究科, 教授 (90126425)
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| Co-Investigator(Kenkyū-buntansha) |
TERASHIMA Tatsuo Tokyo Medical and Dental University, Biostructural Science, Associate Professor, 大学院・医歯学総合研究科, 助教授 (20114770)
BABA Otto Tokyo Medical and Dental University, Biostructural Science, Research Associate, 大学院・医歯学総合研究科, 助手 (90251545)
NAKANO Yukiko Tokyo Medical and Dental University, Biostructural Science, Research Associate, 大学院・医歯学総合研究科, 助手 (20345309)
坂本 裕次郎 東京医科歯科大学, 大学院・医歯学総合研究科, 助手 (90242205)
高橋 信之 生化学工業(株), 東京研究所, 研究員
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | dentin / cementum / regeneration / periodontal ligament / non-collagenous dentin matrix / bisphosphonates / HEBP / tooth / DSP / bisphosphonate |
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| Research Abstract |
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
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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
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