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    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.


    Seyoung Koo, Eun Jung Lee, Hao Xiong, Da Hyeon Yun, Michelle M McDonald, Serk In Park, Jong Seung Kim. Real-Time Live Imaging of Osteoclast Activation via Cathepsin K Activity in Bone Diseases. Angewandte Chemie (International ed. in English). 2024 Feb 05;63(6):e202318459

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    PMID: 38105412

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