Development of fluorescent probe for imaging cell functions involved in bone metabolism

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K05747
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Osaka University
• Principal Investigator: Minoshima Masafumi 大阪大学, 大学院工学研究科, 准教授 (20600844)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 蛍光プローブ / 骨細胞 / pH応答性色素 / 二光子励起 / ケージド化合物

Outline of Final Research Achievements

To better elucidate the function of osteocytes, which play a vital role in bone metabolism, we have successfully developed a fluorescent probe capable of reaching deep bone tissue where osteocytes are located. This probe exhibits fluorescence in low pH environments, allowing us to detect bone resorption by osteocytes. Using two-photon excitation microscopy, we found the disc-shaped fluorescence signals from osteocytic lacunae in living mice, suggesting that osteocytes may produce acid in bone resorption.

During the course of this research, we synthesized a photolabile protecting group under visible light irradiation. We developed a caged glutamic acid with the visible-light responsive protective group. Notably, we have demonstrated visible light regulation of ion channel activity of NMDA-type glutamate receptors.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

骨の代謝異常は骨疾患や免疫系の疾患に関与しており、今回開発した蛍光プローブによって骨細胞の溶解メカニズムをはじめとした未解明の機能の理解が進められるものと期待する。また、骨疾患の治療薬のスクリーニング法にも応用できるものと考える。
可視光応答型ケージド化合物の開発は、神経細胞の光応答の深部における範囲を拡張できることが期待される。また、薬剤を連結することで、長波長光の放出を利用した治療法への応用も可能と考える。