Functional role and signaling pathway of LRP1 in regeneration of periodontal tissue

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09941
• 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: NINOMIYA Tadashi 日本大学, 歯学部, 准教授 (00360222)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: LRP1 / 歯根膜細胞 / 歯周組織形成 / leptin receptor

Outline of Final Research Achievements

This study aimed to demonstrate the function and signaling pathway of low-density lipoprotein receptor-related protein 1 (LRP1). LRP1 was strongly expressed in leptin receptor (Lepr)-positive cells, which are periodontal ligament stem cells. Conditional knockout mice lacking LRP1 in Lepr-positive cells, were inhibited osteoblast differentiation of periodontal ligament cells and decreased ability of bone formation. In addition, LRP1 deficiency suppressed the phosphorylation of Smad1/5/9, a BMP signaling pathway, suggesting that osteoblast differentiation was inhibited and bone formation was reduced. Therefore, LRP1 in Lepr-positive cells promotes osteoblast differentiation and bone formation by activating BMP signaling.

Free Research Field

口腔組織学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、LRP1は骨芽細胞分化を制御するため歯周組織形成に必要な分子であることが示された。歯周炎治療や歯の矯正移動では、歯根膜細胞による骨形成能が必須となっている。これらの治療および処置において、LRP1を制御することで、より効率的な手法の構築が可能になる。また、本研究で得られた結果は、LRP1の新たな機能を示しており、歯科領域のみならず、骨折治癒など整形外科領域、また生化学分野の発展に貢献できると考えられる。