Real-Time Live Imaging of Osteoclast Activation via Cathepsin K Activity in Bone Diseases
Prof. Seyoung Koo
Department of Chemistry, Korea University, Seoul, 02841 Korea
Department of Biomedical and Chemical Sciences, Hyupsung University, Hwaseong, 18330 Korea
These authors contributed equally to this work.
Search for more papers by this authorDr. Eun Jung Lee
Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841 Korea
These authors contributed equally to this work.
Search for more papers by this authorDr. Hao Xiong
Department of Chemistry, Korea University, Seoul, 02841 Korea
Search for more papers by this authorDa Hyeon Yun
Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841 Korea
Search for more papers by this authorProf. Michelle M. McDonald
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
Search for more papers by this authorCorresponding Author
Prof. Serk In Park
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
Search for more papers by this authorCorresponding Author
Prof. Jong Seung Kim
Department of Chemistry, Korea University, Seoul, 02841 Korea
TheranoChem Incorporation, Seoul, 02856 Korea
Search for more papers by this authorProf. Seyoung Koo
Department of Chemistry, Korea University, Seoul, 02841 Korea
Department of Biomedical and Chemical Sciences, Hyupsung University, Hwaseong, 18330 Korea
These authors contributed equally to this work.
Search for more papers by this authorDr. Eun Jung Lee
Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841 Korea
These authors contributed equally to this work.
Search for more papers by this authorDr. Hao Xiong
Department of Chemistry, Korea University, Seoul, 02841 Korea
Search for more papers by this authorDa Hyeon Yun
Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841 Korea
Search for more papers by this authorProf. Michelle M. McDonald
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
Search for more papers by this authorCorresponding Author
Prof. Serk In Park
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
Search for more papers by this authorCorresponding Author
Prof. Jong Seung Kim
Department of Chemistry, Korea University, Seoul, 02841 Korea
TheranoChem Incorporation, Seoul, 02856 Korea
Search for more papers by this authorAbstract
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.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
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