ArticleArthritis research & therapy2012
Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage.
Article in Arthritis research & therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 75 citations in OpenAlex.
- Signal-driven interplay between lipid peroxidation and ferroptosis orchestrates osteoarthritis degeneration.Journal of orthopaedic translation · 2026Review
- The activity "blind spot": Why understanding which proteinases are active, not merely present, is essential for rigorous osteoarthritis research.Osteoarthritis and cartilage · 2026Review
- TRAP5 Inhibition Targeting Scar-Associated Macrophages Ameliorates Acute Kidney Injury to Chronic Kidney Disease Transition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cathepsin K Inhibitors as Potential Drugs for the Treatment of Osteoarthritis.International journal of molecular sciences · 2025Review
- Cartilage Collagen Neoepitope C2C Expression in the Articular Cartilage and Its Relation to Joint Tissue Damage in Patients with Knee Osteoarthritis.Biomedicines · 2024Article
- How are Aging and Osteoarthritis Related?Aging and disease · 2023Review
- Anti-Osteoarthritic Effects of Prunella Vulgaris and Gentiana Lutea In Vitro and In Vivo.Antioxidants (Basel, Switzerland) · 2022Article
- Highly potent inhibitors of cathepsin K with a differently positioned cyanohydrazide warhead: structural analysis of binding mode to mature and zymogen-like enzymes.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Neoepitope fragments as biomarkers for different phenotypes of intervertebral disc degeneration.JOR spine · 2022Article
- Evaluation of enzymatic proteoglycan loss and collagen degradation in human articular cartilage using ultrashort echo time-based biomarkers: A feasibility study.NMR in biomedicine · 2022Article
- Injectable amnion hydrogel-mediated delivery of adipose-derived stem cells for osteoarthritis treatment.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Emerging microfluidics-enabled platforms for osteoarthritis management: from benchtop to bedside.Theranostics · 2022Review
- Autologous protein solution: a promising solution for osteoarthritis?EFORT open reviews · 2021Review
- Changes of type II collagenase biomarkers on IL-1β-induced rat articular chondrocytes.Experimental and therapeutic medicine · 2021Article
- High-Frequency Near-Infrared Diode Laser Irradiation Attenuates IL-1β-Induced Expression of Inflammatory Cytokines and Matrix Metalloproteinases in Human Primary Chondrocytes.Journal of clinical medicine · 2020Article
- Hyaluronan suppresses enhanced cathepsin K expression via activation of NF-κB with mechanical stress loading in a human chondrocytic HCS-2/8 cells.Scientific reports · 2020Article
- Cathepsin K: The Action in and Beyond Bone.Frontiers in cell and developmental biology · 2020Review
- Regulatory mechanisms and clinical manifestations of musculoskeletal aging.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2019Review
- Recent advances in understanding the regulation of metalloproteinases.F1000Research · 2019Review
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Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
introductionThe intra-helical cleavage of type II collagen by proteases, including collagenases and cathepsin K, is increased with aging and osteoarthritis (OA) in cartilage as determined by immunochemical assays. The distinct sites of collagen cleavage generated by collagenases and cathepsin K in healthy and OA human femoral condylar cartilages were identified and compared.
methodsFixed frozen cartilage sections were examined immunohistochemically, using antibodies that react with the collagenase-generated cleavage neoepitopes, C2C and C1,2C, and the primary cleavage neoepitope (C2K) generated in type II collagen by the action of cathepsin K and possibly by other proteases, but not by any collagenases studied to date.
resultsIn most cases, the staining patterns for collagen cleavage were similar for all three epitopes: weak to moderate mainly pericellular staining in non-OA cartilage from younger individuals and stronger, more widespread staining in aging and OA cartilages that often extended from the superficial to the mid/deep zone of the tissue. In very degenerate OA specimens, with significant disruption of the articular surface, staining was distributed throughout most of the cartilage matrix.
conclusionsCleavage of collagen by proteases usually arises pericellularly around chondrocytes at and near the articular surface, subsequently becoming more intense and extending progressively deeper into the cartilage with aging and OA. The close correspondence between the distributions of these products suggests that both collagenases and cathepsin K, and other proteases that may generate this distinct cathepsin K cleavage site, are usually active in the same sites in the degradation of type II collagen.
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Registered trials
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