ArticlePain reports2018
Analgesic effects of the cathepsin K inhibitor L-006235 in the monosodium iodoacetate model of osteoarthritis pain.
Article in Pain reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Cathepsin K Inhibitors as Potential Drugs for the Treatment of Osteoarthritis.International journal of molecular sciences · 2025Review
- Validity evaluation of a rat model of monoiodoacetate-induced osteoarthritis with clinically effective drugs.BMC musculoskeletal disorders · 2024Article
- Latest insights in disease-modifying osteoarthritis drugs development.Therapeutic advances in musculoskeletal disease · 2023Review
- Role of cathepsin K in the expression of mechanical hypersensitivity following intra-plantar inflammation.Scientific reports · 2022Article
- The current state of the osteoarthritis drug development pipeline: a comprehensive narrative review of the present challenges and future opportunities.Therapeutic advances in musculoskeletal disease · 2022Review
- Disease-modifying therapeutic strategies in osteoarthritis: current status and future directions.Experimental & molecular medicine · 2021Review
- New Trends in Pharmacological Treatments for Osteoarthritis.Frontiers in pharmacology · 2021Review
- Development of Postoperative Pain in Patients with End-Stage Knee Osteoarthritis Is Associated with Upregulation of Genes Related to Extracellular Matrix Degradation, Inflammation, and Apoptosis Measured in the Peripheral Blood before Knee Surgery.Life (Basel, Switzerland) · 2020Article
- Lysosomes as a therapeutic target.Nature reviews. Drug discovery · 2019Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe mounting evidence that osteoclasts play an important role in osteoarthritis (OA) pain lead us to investigate the effects of L-006235, a potent and selective inhibitor of cathepsin K, on pain behaviour and joint pathology in a model of OA pain.
methodsEffects of preventative (30 and 100 mg/kg) and therapeutic (100 mg/kg) oral dosing with L-006235 on weight-bearing asymmetry, hind paw withdrawal thresholds, cartilage and bone pathology, synovial inflammation, and drug exposure were studied in the monosodium iodoacetate rat model of OA pain.
resultsPreventative L-006235 inhibited weight-bearing asymmetry from day 14, with this measure nearly abolished by the higher dose. In the same treatment setting, L-006235 prevented lowering of hind paw withdrawal thresholds from day 7. Exposure to L-006235 in plasma was higher for the 100 mg/kg dose, compared with 30 mg/kg. Therapeutic dosing with L-006235 from day 14 significantly inhibited weight-bearing asymmetry, compared with monosodium iodoacetate vehicle rats. Regression analysis revealed a significant interaction coefficient of the effects of L-006235 on weight-bearing asymmetry and synovitis score, but not for cartilage damage nor osteophyte scores.
conclusionOur novel finding that cathepsin K inhibition is analgesic in a clinically relevant model of OA pain provides new evidence for the therapeutic potential of this target.
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