ArticleBone reports2018
Effect of a cathepsin K inhibitor on arthritis and bone mineral density in ovariectomized rats with collagen-induced arthritis.
Article in Bone reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Bridging the gap in OA therapeutics: Bioengineered strategies to target osteoclast-chondrocyte crosstalk.Bioengineering & translational medicine · 2026Review
- EphB4-decorated biomimetic nanoparticles enhance osteoclast targeting and therapeutic effect in osteoporosis.Journal of nanobiotechnology · 2026Article
- Cathepsin K Inhibitors as Potential Drugs for the Treatment of Osteoarthritis.International journal of molecular sciences · 2025Review
- An overview of multi-omics technologies in rheumatoid arthritis: applications in biomarker and pathway discovery.Frontiers in immunology · 2024Review
- Cathepsin K in Pathological Conditions and New Therapeutic and Diagnostic Perspectives.International journal of molecular sciences · 2022Review
- Effects of Metabolic Disorders in Immune Cells and Synoviocytes on the Development of Rheumatoid Arthritis.Metabolites · 2022Review
- Rheumatoid arthritis and mitochondrial homeostasis: The crossroads of metabolism and immunity.Frontiers in medicine · 2022Review
- MicroRNAs in Serum Exosomes as Circulating Biomarkers for Postmenopausal Osteoporosis.Frontiers in endocrinology · 2022Article
- Cathepsin KFrontiers in cell and developmental biology · 2022Review
- Cathepsin K deficiency promotes alveolar bone regeneration by promoting jaw bone marrow mesenchymal stem cells proliferation and differentiation via glycolysis pathway.Cell proliferation · 2021Article
- Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Cathepsin K: The Action in and Beyond Bone.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesCathepsin K is expressed by osteoclasts and synovial fibroblasts and degrades key components of bone and cartilage. Inhibition of cathepsin K protease activity may be beneficial for the prevention of bone erosion and cartilage degradation in rheumatoid arthritis (RA). The collagen-induced arthritis (CIA) rat model is well established for studying the pathology and treatment of RA. We investigated the effect of ONO-KK1-300-01, a cathepsin K inhibitor (CKI), on arthritis and bone mineral density (BMD) in rats with CIA.
methodsSeven-month-old female Sprague Dawley rats were divided into 5 groups: rats without CIA (CNT); CIA rats that underwent ovariectomy (OVX) and were treated with CKI; CIA rats that underwent OVX and were treated with vehicle (Veh); CIA rats that underwent sham surgery and were treated with CKI; and CIA rats that underwent sham surgery and were treated with Veh. CKI was orally administered at a dose of 15 mg/kg, thus initiating collagen sensitization, until death at 4 weeks. We evaluated hind paw thickness and the arthritis score every week until death. Radiographs of the resected left foot were obtained with a soft X-ray apparatus. Destruction of bone and cartilage was classified and scored as previously described by Engelhardt et al. BMD was measured by bone densitometry at the halfway point between the distal metaphysis and the diaphysis of the resected right femur. We also performed histomorphometry of the proximal left tibia, histological evaluation of arthritis, and a bone strength test.
resultsCKI administration significantly reduced hind paw thickness and the arthritis score, and prevented a decrease in BMD. The radiographic score was significantly lower in the CKI group than in the Veh group. In the histomorphometric analysis, bone-resorption parameters were significantly lower in the CKI groups than in the Veh groups. CKI significantly inhibited synovial proliferation in the CIA rats. In the bone strength test, the ultimate stress was significantly higher in the CKI groups than in the Veh groups.
conclusionOur findings indicate that cathepsin K inhibitors may inhibit systemic and local bone loss, ameliorate arthritis, and attenuate the decrease of bone strength in an animal model of arthritis.
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