Study on novel methods to promote bone elongation through intracellular Ca2+ in chondrocytes and treatment of bone system diseases

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19565
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kyoto University
• Principal Investigator: Ichimura Atsuhiko 京都大学, 薬学研究科, 助教 (10609209)
• Co-Investigator(Kenkyū-buntansha): 植田 洋平 京都大学, 医学研究科, 特定助教 (30848213) ; 井貫 晋輔 京都大学, 薬学研究科, 准教授 (70736272)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 軟骨内骨化 / 細胞内Ca2+ / C型ナトリウム利尿ペプチド / 軟骨無形成症

Outline of Final Research Achievements

The following key results were obtained from the analysis of intracellular Ca2+ regulation mechanisms in endochondral ossification using an original Ca2+ imaging system: 1) We found that C-type natriuretic peptide (CNP) activates intracellular Ca2+ signaling in growth plate chondrocytes and identified novel signaling pathways, including TRPM7 and BK channels, that are associated with CNP's bone elongation-promoting effects. 2) We newly found that phosphodiesterase (PDE)3 inhibitors elongate metatarsal bone by activating CNP-activated intracellular Ca2+ signaling pathways.

Free Research Field

分子薬理学

Academic Significance and Societal Importance of the Research Achievements

細胞内Ca2+シグナルは多彩な細胞機能を制御しており、その破綻は様々な疾患の原因となる。長骨伸長を担う軟骨細胞内Ca2+胴体やその制御分子機構はそのほとんどが不明であrい、分子機序の解を目指す本研究の学術的意義は高い。また、本研究によって明らかとなった軟骨細胞内Ca2+シグナルを構築する分子機序は、CNPの新規シグナル経路を踏まえた新たな骨伸長促進薬開発に資する知見を得るに至っており、医薬領域への波及効果を有している。