Elucidation of the molecular mechanisms associated with pathogeny of Crouzon syndrome and drug discovery
| Project/Area Number |
18K09626
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 57040:Regenerative dentistry and dental engineering-related
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| Research Institution | The Nippon Dental University |
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Principal Investigator |
TORII Daisuke 日本歯科大学, 生命歯学部, 講師 (10548259)
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| Co-Investigator(Kenkyū-buntansha) |
筒井 健夫 日本歯科大学, 生命歯学部, 教授 (70366764)
堀江 哲郎 日本歯科大学, 生命歯学部, 講師 (10508675)
小林 朋子 日本歯科大学, 生命歯学部, 講師 (10548283)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | Crouzon症候群 / 頭蓋縫合早期癒合症候群 / FGFR2 / MAPキナーゼ / ゲノム編集 / 頭蓋縫合早期癒合症 / 一塩基置換 / エクソンノックイン |
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| Outline of Final Research Achievements |
Crouzon syndrome (CS) is an inherited craniosynostosis that presents with cranial deformity, hypoplastic maxilla and exophthalmos associated with fibroblast growth factor receptor (FGFR) 2 mutation. In this study, we aimed to solve the molecular mechanisms associated with pathogeny of CS, and to search a new drug.
We evaluated multipotency of CS patient-derived dental pulp stem cells (CS-DPSCs). CS-DPSCs showed multipotency equivalent to healthy donor DPSCs. We investigated the levels of mRNA expression related to mineralization and the phosphorylation rate of mitogen-activated protein kinases (MAPK). High expression of mineralization-related genes were detected in CS-DPSCs compared with in healthy donor DPSCs. Activation of protein kinase C induced a lower phosphorylation rate of MAPK in CS-DPSCs than healthy donor DPSCs.
We performed splice variant analysis toward the RNA-guided genome editing of FGFR2 in DPSCs due to analyze the molecular mechanisms compared with unedited DPSCs.
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| Academic Significance and Societal Importance of the Research Achievements |
頭蓋縫合早期癒合症候群の疾患モデルにおけるこれまでの研究では遺伝子変異箇所の修復が困難であったのに対し、ゲノム編集と部位特異的組換えとの併用によって、原因となる変異箇所を修復し正常な細胞機能の回復を図ることが、本研究課題の学術的意義であると考えられる。
また、得られた細胞試料における分子動態を、クラウド型ナレッジベースへアップロードすることで、Crouzon症候群における症状の発症抑制にはたらく新規治療用薬剤選出につながることが、本研究課題の社会的意義であると考えられる。
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Report
(5 results)
Research Products
(4 results)
