2023 Fiscal Year Final Research Report
Development of new pharmaceutical protein preparations for mineralized tissue regeneration using electric charge mechanism
Project/Area Number |
21K17018
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 57040:Regenerative dentistry and dental engineering-related
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Research Institution | Tohoku University |
Principal Investigator |
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Keywords | 骨 / セメント質 / 歯周組織 / 再生医療 / リン酸/ピロリン酸代謝 / 帯電効果 / アルカリフォスファターゼ |
Outline of Final Research Achievements |
To develop new starategy for mineralized tissue regeneration, we have focused on tissue-nonspecific alkaline phosphatase (TNAP) which is isozyme of alkaline phosphatase (ALP) and promotes biological apatite crystallization. An acidic oligopeptide-tagging approach generated negatively charged TNAP resulting in more efficient delivery to positively charged mineralized tissue. This study aimed to determine the effects of TNAP tagged with 6 or 8 aspartic acid residues (Asp;Asp TNAP) on mineralized tissue regeneration. This study demonstrated that Asp TNAP successfully promoted mineralization and periodontal tissue regeneration in periodontis mouse model. Furthermore, recombinant TNAP significantly inhibited inflammation peridontitis mouse model. This study suggested that electrically charged TNAP is a therapeutic agent that can be applied for mineralized tissue regeneration including periodontal tissue regeneration.
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Free Research Field |
補綴歯科学
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Academic Significance and Societal Importance of the Research Achievements |
世界に先駆けて超高齢化社会を迎えた日本において、歯周炎や骨粗鬆症等の硬組織疾患に罹患する患者が急増している。これまでの硬組織疾患治療薬は、限られた細胞種やメカニズムを標的にした薬剤が多く、硬組織代謝を阻害してしまうことにより、骨壊死や意図しない臓器の石灰化による機能不全等、多くの副作用が報告されている。本研究により、骨代謝を促進して石灰化を促すTNAPの有効性と、帯電効果による硬組織結合力付与という画期的な方法により、新たな硬組織再生療法の可能性が示唆された。今後、安定的製造方法や効果的な投与方法を確立し、新規硬組織再生療法の確立を図る。
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