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

Research output: Contribution to journalArticle

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 languageEnglish
JournalAngewandte Chemie - International Edition
DOIs
Publication statusAcceptance date - 3 Aug 2020

Keywords

  • fluorescent probes
  • intravital imaging
  • osteocytes
  • osteocytic lacunae
  • pH-activatable probes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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