Investigation of novel factors that interact with lamin A in osteocytes

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09999
• 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: Nihon University
• Principal Investigator: TAKAHASHI Tomihisa 日本大学, 歯学部, 教授 (40246905)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Lamin A / 骨細胞 / Wnt/βcatenin / シグナル伝達

Outline of Final Research Achievements

To define the effect of a nuclear protein lamin A, a full length lamin A cDNA was overexpressed in osteocyte-like cell line MLO-Y4, Y4-lamin A (+), and mRNA and protein expressions were compared between Y4-lamin A (+) and control cells, Y4-Wt, which only vector was expressed. Increased expressions of BMP-1, -2, -6, axin, GSK-3β, Wnt and β-catenin were detected Y4-lamin A (+) compared to those of Y4-Wt. Furthermore, the expression levels of OPG and IL-6 in Y4-lamin A (+) were higher than those in Y4-Wt. Microarray analysis detected the increased approximate 1,200 genes and the decreased approximate 800 genes in Y4-lamin A (+) compared to Y4-Wt. These results suggest that lamin A regulated osteocytes function and stimulate osteoclasts differentiation indirectly.

Free Research Field

解剖学

Academic Significance and Societal Importance of the Research Achievements

骨細胞は，骨芽細胞や破骨細胞に直接働きかけ，骨の恒常性維持に重要な役割を演じている。Lamin Aが骨細胞におけるBMP-1，－2，-6の発現を誘導することから，骨組織内での骨芽細胞分化を促進させる因子と考えられる。また，Wnt/β-cateninシグナルの活性化とも関係し，その下流で機能するBMPファミリーをはじめとする様々な因子の発現と骨芽細胞の機能を調整していることが示唆された。本研究で得られた結果は，lamin Aが骨細胞の機能維持にとって重要な因子であるとともに，早老症における骨細胞の機能不全を密接に関連づけた。