Evidence to suggest that cathepsin K degrades articular cartilage in naturally occurring equine osteoarthritis.
Abstract: The mechanisms leading to degeneration of articular cartilage in osteoarthritis (OA) are complex and not yet fully understood. Cathepsin K (CK) is a cysteine protease which can also cleave the triple helix of type II collagen. This exposes a neoepitope that can now be identified by specific antibodies. The aim of this study was to obtain evidence suggesting a role for CK in naturally occurring equine OA in both lesional and peri-lesional regions. Methods: Articular cartilages (n=12 horses; 5 healthy, 7 OA) were harvested from animals postmortem. A gross macroscopic examination, histologic (Safranin O-Fast Green and Picrosirius red staining) and immunohistochemical evaluation were performed. Samples were divided into normal appearing cartilage, peri-lesional and lesional cartilage. Cartilage degradation in the samples was graded histologically and immunohistochemically. CK and possible CK cleavage were detected immunohistochemically with specific anti-protein and anti-neoepitope antibodies, respectively. A comparison of CK neoepitope (C2K) production with the collagenase-generated neoepitope produced by matrix metalloproteinases (MMP)-1, 8 and 13 (C2C) was also assessed immunohistochemically. Results: CK and CK cleavage were significantly more abundant in OA cartilage (both peri-lesional and lesional) when compared to remote cartilage within the sample joint or cartilage from healthy joints. The immunohistochemical pattern observed for CK degradation (C2K) was similar to that of collagenase degradation (C2C). Macroscopic cartilage changes and histologic findings were significantly correlated with immunohistochemistry results. Conclusions: The data generated suggests that CK may be involved in cartilage collagen degradation in naturally occurring osteoarthritis.
Publication Date: 2008-09-21 PubMed ID: 18809344DOI: 10.1016/j.joca.2008.07.017Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The researchers are investigating how the protein Cathepsin K (CK) might contribute to the degradation of joint cartilage (a key feature of osteoarthritis) in horses. They found that CK and the signs of CK breaking down cartilage were more abundant in osteoarthritic cartilage compared to healthy cartilage.
Study Objective and Methodology
- The study aimed to build evidence indicating a role for Cathepsin K (CK) in the degradation of joint cartilage in equine osteoarthritis. CK is a protease, an enzyme that can break down proteins. In this case, CK can break down type II collagen, a major component of cartilage. This results in the exposure of a new molecule, or neoepitope, which can be detected by specific antibodies and thus reveal the presence and activity of CK.
- To conduct their research, the team harvested articular cartilage from 12 horses postmortem – 5 healthy horses and 7 horses with osteoarthritis. They conducted a macroscopic examination, histological staining, and immunohistochemical evaluation to study the pathology of the cartilage and detect the CK neoepitope (C2K). The samples were grouped into ‘normal appearing cartilage’, ‘peri-lesional’, and ‘lesional’ cartilage. Additionally, they compared CK neoepitope production to that of another neoepitope produced by matrix metalloproteinases (MMP)-1, 8, and 13 (C2C).
Study Findings
- The results indicate that CK and CK cleavage were significantly more prevalent in osteoarthritic cartilage (both peri-lesional and lesional) as compared to cartilage from within healthy joints. The pattern of CK degradation (indicated by C2K) was similar to that of collagenase degradation (indicated by C2C).
- Macroscopic cartilage changes and histologic findings correlated significantly with immunohistochemistry results. This further supports the evidence that CK may play a role in the degradation of cartilage collagen in naturally occurring osteoarthritis.
Conclusions
- The data from this research suggests that the protein CK may play a key role in the degradation of cartilage collagen in osteoarthritis. This knowledge could be further leveraged for the development of therapeutic approaches aimed at halting or slowing down the progression of osteoarthritis in horses.
Cite This Article
APA
Vinardell T, Dejica V, Poole AR, Mort JS, Richard H, Laverty S.
(2008).
Evidence to suggest that cathepsin K degrades articular cartilage in naturally occurring equine osteoarthritis.
Osteoarthritis Cartilage, 17(3), 375-383.
https://doi.org/10.1016/j.joca.2008.07.017 Publication
Researcher Affiliations
- Département des sciences cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, St. Hyacinthe, Québec, Canada.
MeSH Terms
- Animals
- Carpus, Animal
- Cartilage, Articular / enzymology
- Cartilage, Articular / pathology
- Cathepsin K
- Cathepsins / metabolism
- Collagen Type II / metabolism
- Collagenases / metabolism
- Epitopes / analysis
- Female
- Horse Diseases / enzymology
- Horse Diseases / pathology
- Horses
- Male
- Osteoarthritis / enzymology
- Staining and Labeling
Citations
This article has been cited 13 times.- Khoshdel A, Forootan M, Afsharinasab M, Rezaian M, Abbasifard M. Assessment of the circulatory concentrations of cathepsin D, cathepsin K, and alpha-1 antitrypsin in patients with knee osteoarthritis. Ir J Med Sci 2023 Jun;192(3):1191-1196.
- Boyde A. The Bone Cartilage Interface and Osteoarthritis. Calcif Tissue Int 2021 Sep;109(3):303-328.
- Nwosu LN, Gowler PRW, Burston JJ, Rizoska B, Tunblad K, Lindström E, Grabowska U, Li L, McWilliams DF, Walsh DA, Chapman V. Analgesic effects of the cathepsin K inhibitor L-006235 in the monosodium iodoacetate model of osteoarthritis pain. Pain Rep 2018 Nov;3(6):e685.
- Hussein H, Boyaka P, Dulin J, Russell D, Smanik L, Azab M, Bertone AL. Cathepsin K Localizes to Equine Bone In Vivo and Inhibits Bone Marrow Stem and Progenitor Cells Differentiation In Vitro. J Stem Cells Regen Med 2017;13(2):45-53.
- Kyostio-Moore S, Piraino S, Berthelette P, Moran N, Serriello J, Bendele A, Sookdeo C, Nambiar B, Ewing P, Armentano D, Matthews GL. Overexpression of cystatin C in synovium does not reduce synovitis or cartilage degradation in established osteoarthritis. Arthritis Res Ther 2015 Jan 16;17(1):5.
- Hu P, Chen W, Bao J, Jiang L, Wu L. Cordycepin modulates inflammatory and catabolic gene expression in interleukin-1beta-induced human chondrocytes from advanced-stage osteoarthritis: an in vitro study. Int J Clin Exp Pathol 2014;7(10):6575-84.
- Dejica VM, Mort JS, Laverty S, Antoniou J, Zukor DJ, Tanzer M, Poole AR. Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage. Arthritis Res Ther 2012 May 14;14(3):R113.
- Achari Y, Reno CR, Frank CB, Hart DA. Carrageenan-induced transient inflammation in a rabbit knee model: molecular changes consistent with an early osteoarthritis phenotype. Inflamm Res 2012 Aug;61(8):907-14.
- Little CB, Barai A, Burkhardt D, Smith SM, Fosang AJ, Werb Z, Shah M, Thompson EW. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum 2009 Dec;60(12):3723-33.
- Brömme D, Lecaille F. Cathepsin K inhibitors for osteoporosis and potential off-target effects. Expert Opin Investig Drugs 2009 May;18(5):585-600.
- Chaugule S, Yang YS, Sato T, Mayer E, Shim JH. USP8-mediated mitochondrial regulation in osteoclasts is essential for skeletal development. Cell Mol Life Sci 2026 Jan 15;83(1):72.
- Martin WN, Hyde C, Yung A, Taffe R, Patel B, Premkumar A, Bhattaram P, Drissi H, Khan NM. Joint Acidosis and Acid-Sensing Receptors and Ion Channels in Osteoarthritis Pathobiology and Therapy. Cells 2025 Oct 16;14(20).
- Brizuela L, Buchet R, Bougault C, Mebarek S. Cathepsin K Inhibitors as Potential Drugs for the Treatment of Osteoarthritis. Int J Mol Sci 2025 Mar 22;26(7).
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