Real-Time Live Imaging of Osteoclast Activation via Cathepsin K Activity in Bone Diseases
- Authors
- Koo, Seyoung; Lee, Eun Jung; Xiong, Hao; Yun, Da Hyeon; McDonald, Michelle M.; Park, Serk In; Kim, Jong Seung
- Issue Date
- Feb-2024
- Publisher
- John Wiley & Sons Ltd.
- Keywords
- Bone Diseases Mouse Models; Cathepsin K; Fluorogenic Probe; Intravital Two-Photon Imaging; Osteoclast
- Citation
- Angewandte Chemie International Edition, v.63, no.6, pp 1 - 8
- Pages
- 8
- Indexed
- SCIE
SCOPUS
- Journal Title
- Angewandte Chemie International Edition
- Volume
- 63
- Number
- 6
- Start Page
- 1
- End Page
- 8
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/118731
- DOI
- 10.1002/anie.202318459
- ISSN
- 1433-7851
1521-3773
- 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.,A new two-photon fluorogenic probe, CatKP1, has been developed to detect cathepsin K and enable the real-time monitoring of osteoclast activity in hindlimb long bones during pathologic bone loss. This highlights the importance of CatKP1 as a valuable tool for studying aberrant osteoclast behavior and exploring new therapeutic strategies.+image,
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