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An Acid‐Activatable Fluorescence Probe for Imaging Osteocytic Bone Resorption Activity in Deep Bone Cavities
Author(s) -
Hashimoto Ryu,
Minoshima Masafumi,
Kikuta Junichi,
Yari Shinya,
Bull Steven D.,
Ishii Masaru,
Kikuchi Kazuya
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202006388
Subject(s) - chemistry , fluorophore , osteocyte , fluorescence , bone resorption , in vivo , bone matrix , biophysics , diphosphonates , matrix (chemical analysis) , biomedical engineering , anatomy , biochemistry , in vitro , medicine , osteoblast , cartilage , physics , microbiology and biotechnology , chromatography , biology , quantum mechanics
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.