Mechanism by which nuclear molecule G9a regulates master genes involved in cell proliferation and differentiation during osteogenesis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09897
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Tsurumi University
• Principal Investigator: Ideno Hisashi 鶴見大学, 歯学部, 助教 (40435699)
• Co-Investigator(Kenkyū-buntansha): 二藤 彰 鶴見大学, 歯学部, 教授 (00240747) ; 小松 浩一郎 鶴見大学, 歯学部, 非常勤講師 (60153665) ; 中島 和久 鶴見大学, 歯学部, 准教授 (90252692)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 破骨細胞 / Nfatc1 / 骨芽細胞 / Runx2 / G9a

Outline of Final Research Achievements

In this study, we aimed to understand how the nuclear molecule G9a influences the function of specific cell lineage master genes in cells related to bone metabolism. The results showed that knocking down G9a and its loss in the osteoclast lineage did not change the expression of the osteoclast differentiation master gene Nfatc1 and proliferation-related genes. However, it did enhance the expression of Nfatc1-regulated Cathepsin K (Ctsk), resulting in renewed Nfatc1 accumulation on the Ctsk promoter. Additionally, it was observed that G9a and Nfatc1 do not bind directly. These findings suggest that G9a may indirectly regulate Nfatc1 function during progenitor osteoclast differentiation.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

核内分子G9aはH3K9のメチル化を介し、様々な核内タンパク質と相互作用する重要なエピジェネティック修飾因子である。本研究では、G9aがH3K9のメチル化とは異なる仕組みをもって破骨細胞系譜の重要な転写因子NFATc1の機能を調節することによって、破骨細胞形成に抑制的にはたらく新しい可能性が示唆された。