Regulatory mechanism of hedgehog in osteogenic differentiation of human dental pulp stem cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K10189
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57040:Regenerative dentistry and dental engineering-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Chikazu Daichi 東京医科大学, 医学部, 主任教授 (30343122)
• Co-Investigator(Kenkyū-buntansha): 古賀 陽子 東京医科大学, 医学部, 兼任助教 (10392408)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ヒト歯髄幹細胞 / 骨芽細胞 / ヘッジホッグ関連遺伝子 / DPSCs / VCAM1 / GFPT2

Outline of Final Research Achievements

DPSCs have high proliferative and multilineage differentiation potential. However, several studies have indicated that there are individual differences in the potential for osteogenic differentiation, and the factors determining these differences are unknown. The purpose of this study was to designate the genes responsible for the individual differences in DPSCs. We focused on hedgehog associate genes and divided DPSCs into high and low osteogenic differentiation ability groups (HG or LG), and compared the gene expression patterns using RNA-seq. Among these patterns, VCAM1 and GFPT2 were significantly expressed in the HG than in the LG. These results indicated that VCAM1-mediated Ras-MEK-Erk and PI3K/Akt pathways and GFPT2-mediated HBP signaling influences osteogenic differentiation of DPSCs. These findings indicate that DPSCs that highly express VCAM1 and GFPT2 have a high capacity for osteogenic differentiation.

Free Research Field

口腔外科学分野

Academic Significance and Societal Importance of the Research Achievements

ヒト歯髄幹細胞（DPSCs）は高い増殖能と高い多分化能を有する優れた細胞資源である。DPSCsの個体差の原因を解明することは、DPSCsを用いた再生細胞治療の適応範囲を広げることにつながる。本研究では、DPSCsの骨形成分化能の高低を比較し、VCAM1とGFPT2がDPSCsの骨形成分化能を予測するための候補遺伝子であることを示した。未分化状態のDPSCsにおけるVCAM1とGFPT2の発現量を事前に調べることは、骨再生のための同種細胞移植のドナーの選択基準の設定に有用であると考えられる。