Elucidation of osteoblast mineralization mechanism using McCunealbright syndrome iPS cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H03007
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Tokyo 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
• Keywords: GNAS / 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

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.

Free Research Field

再生医学

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、