ArticleBioconjugate chemistry2021
Design and Synthesis of Cathepsin-K-Activated Osteoadsorptive Fluorogenic Sentinel (OFS) Probes for Detecting Early Osteoclastic Bone Resorption in a Multiple Myeloma Mouse Model.
Article in Bioconjugate chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Characterization and validation of a bone metastatic castration-resistant prostate cancer model as a nanomedicine evaluation platform.Theranostics · 2026Article
- Multiple myeloma inhibitory effects of natural compounds: enhancement through nanoparticle carriers.Frontiers in pharmacology · 2025Review
- Development and Application of Reversible and Irreversible Covalent Probes for Human and Mouse Cathepsin-K Activity Detection, Revealing Nuclear Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The emerging role of osteoclasts in the treatment of bone metastases: rationale and recent clinical evidence.Frontiers in oncology · 2024Review
- Novel bisphosphonate-based cathepsin K-triggered compound targets the enthesis without impairing soft tissue-to-bone healing.Frontiers in bioengineering and biotechnology · 2024Article
- Cathepsin K-Activated Probe for Fluoro-Photoacoustic Imaging of Early Osteolytic Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Therapeutic Potential of Targeting the NLRP3 Inflammasome in Rheumatoid Arthritis.Inflammation · 2023Review
- Oral microbial extracellular DNA initiates periodontitis through gingival degradation by fibroblast-derived cathepsin K in mice.Communications biology · 2022Article
- Article
- Exploring the role of cathepsin in rheumatoid arthritis.Saudi journal of biological sciences · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
We describe the design and synthesis of OFS-1, an Osteoadsorptive Fluorogenic Sentinel imaging probe that is adsorbed by hydroxyapatite (HAp) and bone mineral surfaces, where it generates an external fluorescent signal in response to osteoclast-secreted cathepsin K (Ctsk). The probe consists of a bone-anchoring bisphosphonate moiety connected to a Förster resonance energy transfer (FRET) internally quenched fluorescent (IQF) dye pair, linked by a Ctsk peptide substrate, GHPGGPQG. Key structural features contributing to the effectiveness of OFS-1 were defined by structure-activity relationship (SAR) and modeling studies comparing OFS-1 with two cognates, OFS-2 and OFS-3. In solution or when preadsorbed on HAp, OFS-1 exhibited strong fluorescence when exposed to Ctsk (2.5-20 nM). Time-lapse photomicrographs obtained after seeding human osteoclasts onto HAp-coated well plates containing preadsorbed OFS-1 revealed bright fluorescence at the periphery of resorbing cells. OFS-1 administered systemically detected early osteolysis colocalized with orthotopic engraftment of RPMI-8226-Luc human multiple myeloma cells at a metastatic skeletal site in a humanized mouse model. OFS-1 is thus a promising new imaging tool for detecting abnormal bone resorption.
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