Study on the mechanism of the pathogenesis of primary failure of eruption

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K19278
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Showa University
• Principal Investigator: Eri Izumida 昭和大学, 歯学部, 助教 (70783497)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 原発性萌出不全 / iPS細胞 / 副甲状腺ホルモン受容体 / 変異

Outline of Final Research Achievements

While several mutations in the (PTH)-1 receptor (PTH1R) gene are associated with primary failure of eruption (PFE), the mechanism of PFE pathogenesis remained unclear. We established iPS cells from the peripheral blood mononuclear cells of a PFE patient and a non-patient (PFE-iPSC and C-iPSC). Osteoblasts-like cells (OB) were derived from PFE-iPSC and C-iPSC. There was no remarkable difference in OB derived from PFE-iPSC and C-iPSC in the calcification, the expression of marker genes, or the active vitamin D-induced expression of RANKL. However, the RANKL expression induced by the PTH in PFE-iPSC-derived OB was significantly lower than that in C-iPSC-derived OB.

Free Research Field

矯正歯科学

Academic Significance and Societal Importance of the Research Achievements

PFE患者のPTH1R遺伝子に変異が報告されていたが、その変異のPFE発症への関与を説明する研究はなかった。今回、PFE患者iPSCを用いることで、PFE患者のPTH1R遺伝子変異がPFE発症に関与するメカニズムのひとつを明らかにした。すなわち、PFE患者由来iPSCと健常人iPSCから誘導した骨芽細胞様細胞で石灰化や分化マーカーの発現に差はなかったが、PTH応答は前者で低下していた。歯の萌出には破骨細胞分化を誘導するRANKLの発現が必要だが、PTH誘導性のRANKL発現が前者で低下していた。PFE患者では、PTH依存性破骨細胞誘導能が低下し、歯の萌出が阻害されている可能性を示唆する。