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

37 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

Funding

This research was supported by the following grants: Grants‐in‐Aid for Scientific Research (16K01933, 20K05747 to M. Minoshima, 19K17906 to J. Kikuta, 19H056570 to M. Ishii, 18H03935, 19K22255 to K. Kikuchi); Innovative Areas “Frontier Research on Chemical Communications” of Ministry of Education (17H06409); Culture, Sports, Science, and Technology (MEXT) of Japan; CREST, Japan Science and Technology (JST) Agency (JPMJCR15G1 to M. Ishii); PRIME (JP19gm6210005 to J. Kikuta); Japan Agency for Medical Research and Development (AMED) (18he0902005h0004, 17ae0101041h9902, 18fm0208018h0002 to K. Kikuchi); Takeda Science Foundation; JSPS A3 Foresight Program; and JSPS CORE‐to‐CORE Program “Asian Chemical Biology Initiative”; Japan (JSPS)‐UK (RSC) Research Cooperative Program (JPJSBP120195705 to K. Kikuchi); Royal Society International Exchange (IECR3183068 to S. D. Bull).

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

Cite this

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title = "An Acid-Activatable Fluorescence Probe for Imaging Osteocytic Bone Resorption Activity in Deep Bone Cavities",

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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author = "Ryu Hashimoto and Masafumi Minoshima and Junichi Kikuta and Shinya Yari and Bull, \{Steven D.\} and Masaru Ishii and Kazuya Kikuchi",

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AU - Hashimoto, Ryu

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AU - Kikuta, Junichi

AU - Yari, Shinya

AU - Bull, Steven D.

AU - Ishii, Masaru

AU - Kikuchi, Kazuya

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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

Funding

Keywords

ASJC Scopus subject areas

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