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Excessive degradation of type II collagen in articular cartilage in equine osteochondrosis.

Abstract: Articular osteochondrosis (OCD) occurs in both man and animals. The etiology remains to be determined. Studies of OCD lesions in animals may provide clues as to its pathogenesis. The aim of our study was to determine whether there was evidence for increased degradation namely proteoglycan (PG) release and type II collagen cleavage in articular cartilage harvested from OCD lesions. We examined ex vivo explants at post-mortem from equine OCD lesions and macroscopically normal site and age matched cartilage. These were cultured over a 10 day period in serum-free medium. Type II collagen cleavage was measured in articular cartilage and media using an Elisa assay to detect the COL2-3/4C(short) epitope, which is generated on cleavage of the triple helix of type II collagen by collagenases. PG release was measured by a dye-binding assay. Cumulative release of PG and COL2-3/4C(short) and their contents in cartilage at the end of the culture period were determined. In OCD lesions there was a significant increase in type II collagen cleavage by collagenase but no evidence for increase of PG degradation. These findings point to a selective increase in type II collagen cleavage by collagenases, in OCD lesions of the kind observed in osteoarthritis. Further work is needed to determine whether changes represent primary or secondary events in the pathogenesis of OCD.
Publication Date: 2002-12-11 PubMed ID: 12472241DOI: 10.1016/S0736-0266(02)00053-0Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

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The research focuses on the over-degradation of type II collagen in the cartilage of horses suffering from osteochondrosis (OCD), a joint condition. It was found that there was significant collagen breakdown in the affected cartilage, similar to what is observed in osteoarthritis, but no significant degradation of proteoglycans was observed in these OCD lesions.

Objectives and methodology of study

  • The study aimed to evaluate whether there was an increased rate of proteoglycan (PG) release and cleavage of type II collagen, a protein providing structural framework in cartilages, in the articular cartilage harvested from OCD lesions. The cause of OCD is not yet fully understood, thus these findings may shed light on its pathogenesis.
  • For the study, ex vivo explants from equine OCD lesions and macroscopically normal cartilage (site and age-matched for accuracy) were examined. These cartilages were cultured over a period of 10 days in serum-free medium.
  • The degree of Type II collagen cleavage was measured in both cartilage and media using an ELISA (enzyme-linked immunosorbent assay) to spot the COL2-3/4C(short) epitope, specifically formed when type II collagen is broken down by collagenases.
  • Additionally, the PG release was measured with a dye-binding assay. The cumulative release of PG and COL2-3/4C(short) and their contents in the cartilage at the end of the culture period were thereafter assessed.

Key Findings

  • The research revealed that in OCD lesions, there was a significant increase in Type II collagen cleavage by collagenase enzymes. This indicates an excessive breakdown of collagen, implying a compromised structure and integrity in the cartilage in these conditions.
  • However, there was no evidence supporting increased degradation of proteoglycans, large molecules that are key to the resilience and elasticity of cartilage. This indicates that this degradation mechanism may not play a significant role in the pathogenesis of OCD in horses.
  • The process observed in OCD lesions was similar to the type of collagenase cleavage seen in osteoarthritis, where there is a deterioration of joint cartilage.
  • This selective increase in type II collagen cleavage by collagenase necessitates further research to understand if these changes are primary causes or secondary outcomes in the development of OCD.

Ideal Next Steps

  • Before the findings can be extrapolated and applied in clinical settings, it is necessary to distinguish whether the observed increased collagen degradation represents a trigger or a resulting factor in the progression of OCD.
  • Continued research can aid in improving the understanding of the exact pathogenesis of OCD and may open up novel therapeutic approaches for managing this joint condition, which is not only seen in horses but also in humans.

Cite This Article

APA
Laverty S, Okouneff S, Ionescu M, Reiner A, Pidoux I, Webber C, Rossier Y, Billinghurst RC, Poole AR. (2002). Excessive degradation of type II collagen in articular cartilage in equine osteochondrosis. J Orthop Res, 20(6), 1282-1289. https://doi.org/10.1016/S0736-0266(02)00053-0

Publication

ISSN: 0736-0266
NlmUniqueID: 8404726
Country: United States
Language: English
Volume: 20
Issue: 6
Pages: 1282-1289

Researcher Affiliations

Laverty, S
  • Faculté de Médecine Vétérinaire, Département de Sciences Cliniques, Université de Montreal, CP 5000, Saint Hyacinthe, Qué., Canada J2S 7C6. sheila.laverty@umontreal.ca
Okouneff, S
    Ionescu, M
      Reiner, A
        Pidoux, I
          Webber, C
            Rossier, Y
              Billinghurst, R C
                Poole, A R

                  MeSH Terms

                  • Animals
                  • Cartilage, Articular / metabolism
                  • Cartilage, Articular / pathology
                  • Cells, Cultured
                  • Collagen Type II / metabolism
                  • Collagenases
                  • Culture Media
                  • DNA / analysis
                  • Female
                  • Horse Diseases / metabolism
                  • Horse Diseases / pathology
                  • Horses
                  • Male
                  • Osteochondritis / metabolism
                  • Osteochondritis / pathology
                  • Osteochondritis / veterinary
                  • Protein Denaturation
                  • Proteoglycans / metabolism

                  Citations

                  This article has been cited 7 times.
                  1. Ignatieva NY, Zakharkina OL, Sviridov AP. Express Analysis of Cartilage Tissue Using Multivariate Analysis of IR Spectra.. Sovrem Tekhnologii Med 2022;14(6):25-32.
                    doi: 10.17691/stm2022.14.6.03pubmed: 37181283google scholar: lookup
                  2. Grissom SK, Semevolos SA, Duesterdieck-Zellmer K. Role of cartilage and bone matrix regulation in early equine osteochondrosis.. Bone Rep 2023 Jun;18:101653.
                    doi: 10.1016/j.bonr.2023.101653pubmed: 36632355google scholar: lookup
                  3. Kornicka K, Al Naem M, Röcken M, Zmiertka M, Marycz K. Osteochondritis Dissecans (OCD)-Derived Chondrocytes Display Increased Senescence, Oxidative Stress, Chaperone-Mediated Autophagy and, in Co-Culture with Adipose-Derived Stem Cells (ASCs), Enhanced Expression of MMP-13.. J Clin Med 2019 Mar 8;8(3).
                    doi: 10.3390/jcm8030328pubmed: 30857162google scholar: lookup
                  4. Wang L, Nissi MJ, Tóth F, Shaver J, Johnson CP, Zhang J, Garwood M, Carlson CS, Ellermann JM. Multiparametric MRI of Epiphyseal Cartilage Necrosis (Osteochondrosis) with Histological Validation in a Goat Model.. PLoS One 2015;10(10):e0140400.
                    doi: 10.1371/journal.pone.0140400pubmed: 26473611google scholar: lookup
                  5. Hellings IR, Ekman S, Hultenby K, Dolvik NI, Olstad K. Discontinuities in the endothelium of epiphyseal cartilage canals and relevance to joint disease in foals.. J Anat 2016 Jan;228(1):162-75.
                    doi: 10.1111/joa.12391pubmed: 26471892google scholar: lookup
                  6. Power J, Hernandez P, Wardale J, Henson FM. Alterations in sclerostin protein in lesions of equine osteochondrosis.. Vet Rec Open 2014;1(1):e000005.
                    doi: 10.1136/vropen-2013-000005pubmed: 26392871google scholar: lookup
                  7. Verwilghen DR, Martens A, Busschers E, Franck T, Deberg M, Henrotin Y, Vanderheyden L, Serteyn D. Coll2-1, Coll2-1NO2 and myeloperoxidase concentrations in the synovial fluid of equine tarsocrural joints affected with osteochondrosis.. Vet Res Commun 2011 Oct;35(7):401-8.
                    doi: 10.1007/s11259-011-9487-5pubmed: 21681550google scholar: lookup