ArticleBritish journal of pharmacology2016
A novel approach to inhibit bone resorption: exosite inhibitors against cathepsin K.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- The Skeletal Effects of Tanshinones: A Review.Molecules (Basel, Switzerland) · 2021Pooled it
- Local Sodium Tanshinone IIA Sulfonate Attenuates Periodontal Bone Loss by Modulating Inflammatory, Immune and Osteoclastogenic Signalling.Journal of clinical periodontology · 2026Article
- Proteolysis at the extracellular matrix interface: Molecular architects and regulators in health and disease.The FEBS journal · 2026Review
- Non-coding RNA modulation in osteoclasts and its implications for osteoblast lineage cell behavior in a co-culture system.Cell communication and signaling : CCS · 2025Article
- Cathepsin K inhibitors promote osteoclast-osteoblast communication and engagement of osteogenesis.JBMR plus · 2025Article
- Therapeutic Potential of Tanshinones in Osteolytic Diseases: From Molecular and Cellular Pathways to Preclinical Models.Dentistry journal · 2025Review
- Small-molecule Cathepsin K inhibitors: a medicinal chemistry perspective.Future medicinal chemistry · 2025Review
- Proteins and DNA Sequences Interacting with Tanshinones and Tanshinone Derivatives.International journal of molecular sciences · 2025Review
- Pharmacological impacts of tanshinone on osteogenesis and osteoclastogenesis: a review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Measuring Calcium Levels in Bone-Resorbing Osteoclasts and Bone-Forming Osteoblasts.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Stage-specific modulation of multinucleation, fusion, and resorption by the long non-coding RNA DLEU1 and miR-16 in human primary osteoclasts.Cell death & disease · 2024Article
- Heparan sulfate selectively inhibits the collagenase activity of cathepsin K.Matrix biology : journal of the International Society for Matrix Biology · 2024Article
- Dysregulated lysosomal exocytosis drives protease-mediated cartilage pathogenesis in multiple lysosomal disorders.iScience · 2024Article
- Real-time analysis of osteoclast resorption and fusion dynamics in response to bone resorption inhibitors.Scientific reports · 2024Article
- Heparan sulfate selectively inhibits the collagenase activity of cathepsin K.bioRxiv : the preprint server for biology · 2024Article
- Salvia miltiorrhiza in osteoporosis: a review of its phytochemistry, traditional clinical uses and preclinical studies (2014-2024).Frontiers in pharmacology · 2024Review
- Cysteine Cathepsins as Therapeutic Targets in Immune Regulation and Immune Disorders.Biomedicines · 2023Review
- Functional Heterogeneity Within Osteoclast Populations-a Critical Review of Four Key Publications that May Change the Paradigm of Osteoclasts.Current osteoporosis reports · 2022Review
- CST6 suppresses osteolytic bone disease in multiple myeloma by blocking osteoclast differentiation.The Journal of clinical investigation · 2022Article
- Puerarin specifically disrupts osteoclast activation via blocking integrin-β3 Pyk2/Src/Cbl signaling pathway.Journal of orthopaedic translation · 2022Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
background and purposeCathepsin K (CatK) is a major drug target for the treatment of osteoporosis. Potent active site-directed inhibitors have been developed and showed variable success in clinical trials. These inhibitors block the entire activity of CatK and thus may interfere with other pathways. The present study investigates the antiresorptive effect of an exosite inhibitor that selectively inhibits only the therapeutically relevant collagenase activity of CatK. EXPERIMENTAL APPROACH: Human osteoclasts and fibroblasts were used to analyse the effect of the exosite inhibitor, ortho-dihydrotanshinone (DHT1), and the active site inhibitor, odanacatib (ODN), on bone resorption and TGF-ß1 degradation. Cell cultures, Western blot, light and scanning electron microscopy as well as energy dispersive X-ray spectroscopy, molecular modelling and enzymatic assays were used to evaluate the inhibitors. KEY
resultsDHT1 selectively inhibited the collagenase activity of CatK, without affecting the viability of osteoclasts. Both inhibitors abolished the formation of resorption trenches, with DHT1 having a slightly higher IC50 value than ODN. Maximal reductions of other resorption parameters by DHT1 and ODN were comparable, respectively 41% and 33% for total resorption surface, 46% and 48% for resorption depths, and 83% and 61% for C-terminal telopetide fragment (CTX) release. DHT1 did not affect the turnover of fibrosis-associated TGF-ß1 in fibroblasts, whereas 500 nM ODN was inhibitory. CONCLUSIONS AND IMPLICATIONS: Our study shows that an exosite inhibitor of CatK can specifically block bone resorption without interfering with other pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.