| 研究課題/領域番号 |
23K09227
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分57040:口腔再生医学および歯科医用工学関連
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| 研究機関 | 愛知学院大学 |
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研究代表者 |
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| 研究分担者 |
本田 雅規 愛知学院大学, 歯学部, 教授 (70361623)
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| 研究期間 (年度) |
2023-04-01 – 2026-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円)
2025年度: 1,950千円 (直接経費: 1,500千円、間接経費: 450千円)
2024年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2023年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
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| キーワード | Autophagy / NLRP3 inflammasome / Dental pulp regeneration / Odontoblasts |
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| 研究開始時の研究の概要 |
Achieving complete and functional dental pulp tissue regeneration remains a challenge. Data shows that autophagy improves dental pulp regeneration by enhancing vascularization. The protein complex, NLRP3 inflammasome, inhibits autophagy, therefore, their role in dental regeneration needs clarification. Thus, we aim to study if NLRP3 inflammasome inhibition promotes odontoblast formation in an extra-oral tooth transplantation model. Using NLRP3-specific inhibitors and histological analysis of dental pulp, the role of NLRP3-autophagy interplay in dental pulp regeneration will be elucidated.
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| 研究実績の概要 |
Our study aims to analyze if by stopping or inhibiting the activity of the NLRP3 inflammasome or just "NLRP3", dental pulp regeneration in teeth transplanted from old mice into a host mouse is improved. Inhibiting NLRP3 would in turn activate autophagy, which has been described to have a role in dental pulp regeneration. We used a molecule called MCC950 which inhibits NLRP3. We first tested the dose and time of MCC950. We used 40 mg/kg of MCC950 orally and applied it daily for 2 weeks in 3-week-old mice and confirmed that NLRP3 activity was reduced by adding 25 mg/kg of LPS (which activates the inflammatory cytokine, IL-1b via NLRP3). Then we measured IL-1b release by ELISA. IL-1b was decreased in MCC950-treated mice compared to untreated controls. However, the difference was not statistically significant.
We also performed extraoral transplantation using immature teeth (open apexes) in GFP host mice. With H&E staining we saw a healing pattern that resembled cementum filling the pulp cavity in the coronal portion and pulp-like tissue in the apical portion. These cells were nestin+ and had GFP expression near it, results that were similar to our previous study.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Although the volume of data is not a lot yet, the initial techniques, such as the extraoral transplantation method and the efficiency of MCC950 have been carried out. The dose of MCC950 could be increased more to obtain a statistical difference in the reduction of IL-1b release. Initial histological data to confirm our previous study`s although more data is necessary for confirmation.
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| 今後の研究の推進方策 |
In this fiscal year, we plan to apply the methodologies described above, which have been confirmed and then test if the inhibition of NLRP3 improves pulp regeneration in teeth with mature roots. We plan to prepare as many samples as necessary while in parallel histologically the samples that are finished as soon as possible. With this we can obtain a large amount of histological data and confirm if other measures are required to test our hypothesis.
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