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An Acid-Activatable Fluorescence Probe for Imaging Osteocytic Bone Resorption Activity in Deep Bone Cavities |
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| Authors: | Ryu Hashimoto Dr. Masafumi Minoshima Dr. Junichi Kikuta Shinya Yari Prof. Steven D. Bull Prof. Masaru Ishii Prof. Kazuya Kikuchi |
| Affiliation: | 1. Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871 Japan;2. Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871 Japan Immunology Frontier Research Center, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871 Japan;3. Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871 Japan;4. Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY UK |
| 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. |
| Keywords: | fluorescent probes intravital imaging osteocytes osteocytic lacunae pH-activatable probes |