학술논문
Real-Time Live Imaging of Osteoclast Activation via Cathepsin K Activity in Bone Diseases.
Document Type
Academic Journal
Author
Koo S; Department of Chemistry, Korea University, Seoul, 02841, Korea.; Department of Biomedical and Chemical Sciences, Hyupsung University, Hwaseong, 18330, Korea.; Lee EJ; Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841, Korea.; Xiong H; Department of Chemistry, Korea University, Seoul, 02841, Korea.; Yun DH; Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841, Korea.; McDonald MM; Skeletal Diseases Program, The Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.; St Vincent's Clinical Campus, School of Clinical Medicine, University of New South Wales, Kensington, NSW, 2052, Australia.; School of Medicine Science, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia.; Park SI; Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841, Korea.; Vanderbilt Center for Bone Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.; Kim JS; Department of Chemistry, Korea University, Seoul, 02841, Korea.; TheranoChem Incorporation, Seoul, 02856, Korea.
Source
Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 0370543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-3773 (Electronic) Linking ISSN: 14337851 NLM ISO Abbreviation: Angew Chem Int Ed Engl Subsets: MEDLINE
Subject
Language
English
Abstract
Intravital fluorescence imaging of functional osteoclasts within their intact disease context provides valuable insights into the intricate biology at the microscopic level, facilitating the development of therapeutic approaches for osteoclast-associated bone diseases. However, there is a lack of studies investigating osteoclast activity within deep-seated bone lesions using appropriate fluorescent probes, despite the advantages offered by the multi-photon excitation system in enhancing deep tissue imaging resolution. In this study, we report on the intravital tracking of osteoclast activity in three distinct murine bone disease models. We utilized a cathepsin K (CatK)-responsive two-photon fluorogenic probe (CatKP1), which exhibited a notable fluorescence turn-on response in the presence of active CatK. By utilizing CatKP1, we successfully monitored a significant increase in osteoclast activity in hindlimb long bones and its attenuation through pharmacological intervention without sacrificing mice. Thus, our findings highlight the efficacy of CatKP1 as a valuable tool for unraveling pathological osteoclast behavior and exploring novel therapeutic strategies.
(© 2023 Wiley-VCH GmbH.)
(© 2023 Wiley-VCH GmbH.)