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Development of the dental epithelial cell differentiation for tooth regeneration using novel small molecule compounds

Research Project

Project/Area Number 16K20631
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Orthodontics/Pediatric dentistry
Research InstitutionKanagawa Children's Medical Center (Clinical Research Institute)

Principal Investigator

Naruse Masahiro  地方独立行政法人神奈川県立病院機構神奈川県立こども医療センター(臨床研究所), 臨床研究所, 医師 (00756273)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords歯の再生 / 細胞分化 / 小分子化合物 / 歯の発生 / 遺伝子発現
Outline of Final Research Achievements

TrkB receptor is considered to have important roles during tooth development including cell proliferation and differentiation. LM22A-4 is a synthetic, selective small-molecule partial agonist of TrkB.
In this study, we demonstrated the biological activities of LM22A-4, in dental epithelial cells. LM22A-4 induced the expression of early marker genes of ameloblasts such as Ameloblastin, Amelogenin, and MMP-20. In dental epithelial cells, ameloblast differentiation is induced by activating ERK1/2 signaling. Time course experiments showed that the peak of phosphorylation of ERK1/2 was observed 10 minutes after LM22A-4 stimulation.These results suggested that LM22A-4 promotes dental epithelial cells differentiation into ameloblasts.

Academic Significance and Societal Importance of the Research Achievements

本研究ではXeno-free培養下での歯原性細胞の安定的供給とエナメル芽細胞分化誘導を目的とし、細胞増殖および分化誘導作用を保持する複数の小分子化合物を組み合わせた、新規の細胞増殖・分化制御ハイブリッド培養法の開発を目指した。本研究で着目したLM22A-4という小分子化合物は歯の細胞の分化誘導に有効であることが示唆され、分化誘導培養法の開発へ有効な知見となったと考えられた。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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