Control of Neural crest stem cell like MSC spheroids with DNA methylation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17KK0182
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Prosthodontics/ Dental materials science and
• Research Institution: Tohoku University
• Principal Investigator: Niibe Kunimichi 東北大学, 大学病院, 助教 (50468500)
• Project Period (FY): 2018 – 2019
• Keywords: エピジェネティクス / 歯原性間葉 / 分化制御

Outline of Final Research Achievements

Studies on human and animal models have demonstrated the complex molecular regulatory network between dental mesenchyme and epithelium governing tooth development. However, epigenetic regulation of tooth development has not been well investigated. The aim of this study was to elucidate the relationship between an epigenetic modifier and dental root development using Hdac3-CKOosx mice. We show that Hdac3 depletion in Osterix expressing dental pulp stem cells, odontoblasts, and cementocytes cause a progressive postnatal obstruction resulting in comparatively short roots and smaller root apices of the molar. We observed degeneration in the histological development of dentin and cementum structures. Dentin and cementum had shaky borders and disordered hematoxylin staining; in addition, the Hdac3-CKOosx had thin cementum compared to that in the wild-type mice. These findings show that Hdac3 is essential in dental mesenchymal cells and regulates the rate of root formation and development.

Free Research Field

再生歯科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、HDAC3抑制もしくは薬剤としてのインヒビターが歯原性間葉組織の成長や分化を抑制、停止する可能性があることが明らかとなった。これら得られた知見は、将来的に歯胚再生が実現した際に、再生歯胚の物理的な大きさや形態を人為的に調整できる可能性を示唆させるこれまでにない成果であると考えられる。
今後、我々が研究している間葉系幹細胞スフェアを歯原性寛間葉に分化することが可能となれば、HDAC3インヒビターをうまく利用することで、その分化を調整できるかを検証していくことを予定している。