Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 47, Pages 20996-21000Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202006388
Keywords
fluorescent probes; intravital imaging; osteocytes; osteocytic lacunae; pH-activatable probes
Categories
Funding
- 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]
- PRIME [JP19gm6210005]
- Japan Agency for Medical Research and Development (AMED) [18he0902005h0004, 7ae0101041h9902, 18fm0208018h0002]
- Takeda Science Foundation
- JSPS A3 Foresight Program
- JSPS CORE-to-CORE Program Asian Chemical Biology Initiative
- Japan (JSPS)-UK (RSC) Research Cooperative Program [JPJSBP120195705]
- Royal Society International Exchange [IEC\R3\183068]
- [16K01933]
- [20K05747]
- [19K17906]
- [19H056570]
- [18H03935]
- [19K22255]
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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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