An Acid-Activatable Fluorescence Probe for Imaging Osteocytic Bone Resorption Activity in Deep Bone Cavities

Ryu Hashimoto; Masafumi Minoshima; Junichi Kikuta; Shinya Yari; Steven D. Bull; Masaru Ishii; Kazuya Kikuchi

doi:10.1002/anie.202006388

An Acid-Activatable Fluorescence Probe for Imaging Osteocytic Bone Resorption Activity in Deep Bone Cavities

Ryu Hashimoto, Masafumi Minoshima, Junichi Kikuta, Shinya Yari, Steven D. Bull, Masaru Ishii, Kazuya Kikuchi

Department of Chemistry

Osaka University

Research output: Contribution to journal › Article › peer-review

29 Citations (SciVal)

Abstract

A rationally designed pH-activatable fluorescent probe (pHocas-RIS) has been used to measure localised pH levels in osteocytic lacunae in bone tissue. Conjugation of the moderate bone-binding drug risedronate to a pH-activatable BODIPY fluorophore enables the probe to penetrate osteocytic lacunae cavities that are embedded deep within the bone matrix. After injection of pHocas-RIS, any osteocytic lacunae caused by bone-resorbing osteocytes cause the probe to fluoresce in vivo, thus allowing imaging by intravital two-photon excitation microscopy. This pH responsive probe enabled the visualization of the bone mineralizing activities of acid producing osteocytes in real time, thus allowing the study of their central role in remodeling the bone-matrix in healthy and disease states.

Original language	English
Pages (from-to)	20996-21000
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	59
Issue number	47
Early online date	3 Aug 2020
DOIs	https://doi.org/10.1002/anie.202006388
Publication status	Published - 16 Nov 2020

Keywords

fluorescent probes
intravital imaging
osteocytes
osteocytic lacunae
pH-activatable probes

ASJC Scopus subject areas

Catalysis
General Chemistry

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10.1002/anie.202006388Licence: CC BY-NC

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abstract = "A rationally designed pH-activatable fluorescent probe (pHocas-RIS) has been used to measure localised pH levels in osteocytic lacunae in bone tissue. Conjugation of the moderate bone-binding drug risedronate to a pH-activatable BODIPY fluorophore enables the probe to penetrate osteocytic lacunae cavities that are embedded deep within the bone matrix. After injection of pHocas-RIS, any osteocytic lacunae caused by bone-resorbing osteocytes cause the probe to fluoresce in vivo, thus allowing imaging by intravital two-photon excitation microscopy. This pH responsive probe enabled the visualization of the bone mineralizing activities of acid producing osteocytes in real time, thus allowing the study of their central role in remodeling the bone-matrix in healthy and disease states.",

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AU - Hashimoto, Ryu

AU - Minoshima, Masafumi

AU - Kikuta, Junichi

AU - Yari, Shinya

AU - Bull, Steven D.

AU - Ishii, Masaru

AU - Kikuchi, Kazuya

PY - 2020/11/16

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KW - fluorescent probes

KW - intravital imaging

KW - osteocytes

KW - osteocytic lacunae

KW - pH-activatable probes

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An Acid-Activatable Fluorescence Probe for Imaging Osteocytic Bone Resorption Activity in Deep Bone Cavities

Abstract

Keywords

ASJC Scopus subject areas

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