ArticleInternational journal of rheumatology2019
Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotrexate on Collagen-Induced Arthritis in Cynomolgus Monkeys.
Article in International journal of rheumatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Proteases and Osteoporosis: A Comprehensive Review of Their Role in Bone Health.Current drug targets · 2025Review
- Inhibition of cysteine protease disturbs the topological relationship between bone resorption and formation in vitro.Journal of bone and mineral metabolism · 2024Article
- Nitrogen-Containing Bisphosphonates Downregulate Cathepsin K and Upregulate Annexin V in Osteoclasts CulturedInternational journal of dentistry · 2023Article
- Cathepsin K in Pathological Conditions and New Therapeutic and Diagnostic Perspectives.International journal of molecular sciences · 2022Review
- Recent advances in developing small-molecule inhibitors against SARS-CoV-2.Acta pharmaceutica Sinica. B · 2022Review
- Therapeutic Treatments for Osteoporosis-Which Combination of Pills Is the Best among the Bad?International journal of molecular sciences · 2022Review
- Cathepsin KFrontiers in cell and developmental biology · 2022Review
- Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy.Signal transduction and targeted therapy · 2021Review
- Cathepsin K: The Action in and Beyond Bone.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We examined whether the cathepsin K inhibitor, ONO-5334, administered alone or in combination with methotrexate (MTX), could ameliorate joint destruction evoked by collagen-induced arthritis (CIA) in female cynomolgus monkeys. CIA was induced by immunizing with bovine type II collagen. ONO-5334 (30 mg/kg/day) was orally administered once daily and MTX (10 mg/body/day) twice weekly for 9 weeks. X-ray (evaluation of joint destruction) and swelling (inflammatory) scores of proximal interphalangeal (PIP), distal interphalangeal (DIP), and metacarpophalangeal (MP) joints were evaluated. Urinary concentrations of C-terminal telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) were measured. Arthritis, accompanied by bone and cartilage destruction, was successfully induced in this collagen-induced arthritis monkey model. ONO-5334 showed no suppressive effect on joint swelling, while the joint swelling scores in the MTX and combination (ONO-5334 + MTX) groups were less than 50% compared with the control group. ONO-5334 decreased X-ray score by a mean of 64% (p<0.05 vs the control group), and MTX also decreased in X-ray score by a mean of 46% but with no statistical significance. Combination of ONO-5334 and MTX further decreased the X-ray score by 28% over MTX group (74% reduction vs the control group, p<0.01). Maximum increase in CTX-I (10-fold) and CTX-II (7-fold) compared to baseline was observed at 7 and 3 weeks after the first sensitization, respectively. After treatment with ONO-5334 alone or in combination with MTX, concentrations were maintained near baseline for both markers. In conclusion, ONO-5334 prevented joint destruction but not joint inflammation in this monkey CIA model. Concomitant use of ONO-5334 with MTX reduced architectural joint destruction compared to MTX alone; therefore, ONO-5334 may help to prevent joint destruction in combination with MTX for the treatment of rheumatoid arthritis.
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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.