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Elucidation of osteoblast mineralization mechanism using McCunealbright syndrome iPS cells

Research Project

Project/Area Number 18H03007
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionTokyo Dental College

Principal Investigator

AZUMA TOSHIFUMI  東京歯科大学, 歯学部, 教授 (00222612)

Co-Investigator(Kenkyū-buntansha) 中村 貴  東京歯科大学, 歯学部, 講師 (80431948)
柴原 孝彦  東京歯科大学, 歯学部, 教授 (50178919)
齋藤 淳  東京歯科大学, 歯学部, 教授 (60266559)
小野寺 晶子  東京歯科大学, 歯学部, 講師 (90637662)
齋藤 暁子  東京歯科大学, 歯学部, 助教 (90722835)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2020: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
KeywordsGNAS / ヘッジホッグ / iPS細胞 / 骨芽細胞 / 骨 / 線維性骨異形成症 / McCune Albright 症候群 / 消化管腫瘍 / Gorlin症候群 / McCuneAlbright症候群 / Hedgehog経路 / 骨代謝 / 骨粗しょう症治療薬 / cAMP / Hedgehog / iPS / 石灰化 / cAMP / マキューンオルブライト症候群 / ヘッジホッグ経路 / GANS / McCune Albright Syndrome
Outline of Final Research Achievements

The pathophysiology of congenital skeletal diseases is diverse, and it has been clarified that disease-specific iPS cell application is important for elucidating the pathophysiological mechanism of the disease. GNAS-rich iPS cells (fibrous dysplasia and McCune-Albright syndrome) iPS cells were generated and compared with Gorlin syndrome ipS cells, with the aim of elucidating the relationship and pathophysiology of the Hedgehog pathway and the GNAS pathway. When GNAS-rich iPS cells were established and neoplastic lesions were reproduced, it was found that the undifferentiated state of diseased cells was enhanced. Therefore, it was clarified that the inhibition of osteoblast differentiation in fibrous dysplasia may be directly linked to the treatment by appropriately correcting the inhibition of Hedgehog by drug administration.

Academic Significance and Societal Importance of the Research Achievements

GNAS過剰変異は Sporadicに発生するMcCuneAlbright syndrome や Fibrous dysplasia など にみられる遺伝子変異であるが その解明においては 上記疾患細胞の獲得が非常に困難であることが 大きな障害となっていた。 本研究にて iPS細胞を作製したことにより この疾患に関連した多くの疾患(線維性骨異形成症、消化管良性腫瘍 膵癌)の研究など広範に利用可能である、

Report

(3 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(3 results)

All 2020

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results)

  • [Journal Article] Tissue-nonspecific alkaline phosphatase promotes the osteogenic differentiation2020

    • Author(s)
      Nakamura T, Nakamura-Takahashi A, Kasahara M, Yamaguchi A, Azuma T.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 524(3) Pages: 702-709

    • DOI

      10.1016/j.bbrc.2020.01.136

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stepwise strategy for generating osteoblasts from human pluripotent stem cells under fully defined xeno-free conditions with small-molecule inducers2020

    • Author(s)
      Zujur Denise、Kanke Kosuke、Onodera Shoko、Tani Shoichiro、Lai Jenny、Azuma Toshifumi、Xin Xiaonan、Lichtler Alexander C.、Rowe David W.、Saito Taku、Tanaka Sakae、Masaki Hideki、Nakauchi Hiromitsu、Chung Ung-il、Hojo Hironori、Ohba Shinsuke
    • Journal Title

      Regen Ther

      Volume: 14 Pages: 19-31

    • DOI

      10.1016/j.reth.2019.12.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stage-dependent differential gene expression profiles of cranial neural2020

    • Author(s)
      Odashima A, Onodera S, Saito A, Ogihara Y, Ichinohe T, Azuma T.
    • Journal Title

      Med Mol Morphol

      Volume: 53(1) Pages: 28-41

    • DOI

      10.1007/s00795-019-00229-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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