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Connective tissue research2008; 49(2); 62-67; doi: 10.1080/03008200801913338

MT3-MMP (MMP-16) is downregulated by in vitro cytokine stimulation of cartilage, but unaltered in naturally occurring equine osteoarthritis and osteochondrosis.

Abstract: Matrix degradation by metalloproteinases is considered a key feature in the loss of articular cartilage seen in many joint diseases. Membrane-type matrix metalloproteinase-3 (MT3-MMP) expression is elevated in human cartilage in end-stage osteoarthritis. We investigated whether MT3-MMP is similarly regulated in cartilage in two naturally occurring arthropathies in vivo and whether proinflammatory cytokines regulate its expression in vitro. MT3-MMP expression was evaluated in cartilage from horses with osteoarthritis and osteochondrosis and compared with age- and site-matched normal cartilage. MT3-MMP also was measured in normal cartilage stimulated with proinflammatory cytokines. MT3-MMP expression was not significantly altered in either osteoarthritis or osteochondrosis cartilage. However, gene expression was significantly downregulated by the addition of recombinant human interleukin-1beta, oncostatin M, or tumor necrosis factor-alpha to normal cartilage explants. The results suggest that MT3-MMP may not have a role in matrix destruction in equine cartilage diseases. Further work is required to characterize its regulation and function.
Publication Date: 2008-04-03 PubMed ID: 18382891DOI: 10.1080/03008200801913338Google Scholar: Lookup
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  • Journal Article

Summary

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The article investigates the role of MT3-MMP, a type of metalloproteinase thought to contribute to joint disease, in horses with osteoarthritis and osteochondrosis, determining that it doesn’t appear to be altered in these conditions. However, these enzymes were found to be downregulated by cytokines, implying they may not be largely involved in the degradation of cartilage in equine disease.

Introduction

  • The study focuses on MT3-MMP (Membrane-type matrix metalloproteinase-3), a metalloproteinase involved in matrix degradation, a critical process observed in many joint diseases.
  • Previous research revealed increased MT3-MMP expression in human cartilage suffering from end-stage osteoarthritis, implying a possible role for this protein in the disease’s progression.

Study Objective

  • The primary goal of the research was to explore whether MT3-MMP is regulated in cartilage similarly in two common arthropathies – osteoarthritis and osteochondrosis – in horses.
  • Another focus was to investigate how proinflammatory cytokines could potentially influence MT3-MMP expression.

Methodology and Findings

  • MT3-MMP expression was analyzed in cartilage samples from horses diagnosed with osteoarthritis and osteochondrosis.
  • These results were then compared with MT3-MMP levels in normal, age-and site-matched horse cartilage.
  • In addition, normal cartilage was subjected to stimulation with proinflammatory cytokines, and then assessed for MT3-MMP quantity.
  • Results showed that MT3-MMP expression was not significantly altered in cartilage from osteoarthritis or osteochondrosis affected horses.
  • However, in vitro studies indicated that proinflammatory cytokines, such as human interleukin-1beta, oncostatin M, or tumor necrosis factor-alpha, could significantly downregulate MT3-MMP gene expression.

Conclusion

  • The findings of this study suggest that MT3-MMP may not have a major role in the matrix destruction witnessed in equine cartilage diseases.
  • The researchers propose further investigation to better understand the regulation and function of MT3-MMP, given these results and established knowledge of its elevated presence in human end-stage osteoarthritis.

Cite This Article

APA
Garvican ER, Vaughan-Thomas A, Redmond C, Clegg PD. (2008). MT3-MMP (MMP-16) is downregulated by in vitro cytokine stimulation of cartilage, but unaltered in naturally occurring equine osteoarthritis and osteochondrosis. Connect Tissue Res, 49(2), 62-67. https://doi.org/10.1080/03008200801913338

Publication

ISSN: 1607-8438
NlmUniqueID: 0365263
Country: England
Language: English
Volume: 49
Issue: 2
Pages: 62-67

Researcher Affiliations

Garvican, E R
  • Musculoskeletal Research Group, University of Liverpool, Wirral, United Kingdom. e.garvican@liv.ac.uk
Vaughan-Thomas, A
    Redmond, C
      Clegg, P D

        MeSH Terms

        • Animals
        • Cartilage, Articular / enzymology
        • Cartilage, Articular / immunology
        • Cartilage, Articular / physiopathology
        • Cells, Cultured
        • Cytokines / drug effects
        • Cytokines / immunology
        • Down-Regulation / drug effects
        • Down-Regulation / immunology
        • Extracellular Matrix / drug effects
        • Extracellular Matrix / immunology
        • Extracellular Matrix / metabolism
        • Gene Expression Regulation / genetics
        • Gene Expression Regulation / immunology
        • Horse Diseases / immunology
        • Horse Diseases / metabolism
        • Horse Diseases / physiopathology
        • Horses
        • Interleukin-1beta / immunology
        • Interleukin-1beta / pharmacology
        • Matrix Metalloproteinase 16 / drug effects
        • Matrix Metalloproteinase 16 / genetics
        • Matrix Metalloproteinase 16 / metabolism
        • Oncostatin M / immunology
        • Oncostatin M / pharmacology
        • Osteoarthritis / enzymology
        • Osteoarthritis / immunology
        • Osteoarthritis / veterinary
        • Osteochondritis / enzymology
        • Osteochondritis / immunology
        • Osteochondritis / veterinary
        • RNA, Messenger / drug effects
        • RNA, Messenger / metabolism
        • Tumor Necrosis Factor-alpha / immunology
        • Tumor Necrosis Factor-alpha / pharmacology

        Citations

        This article has been cited 3 times.
        1. Cheng NT, Guo A, Meng H. The protective role of autophagy in experimental osteoarthritis, and the therapeutic effects of Torin 1 on osteoarthritis by activating autophagy. BMC Musculoskelet Disord 2016 Apr 6;17:150.
          doi: 10.1186/s12891-016-0995-xpubmed: 27052304google scholar: lookup
        2. Peffers MJ, Beynon RJ, Clegg PD. Absolute quantification of selected proteins in the human osteoarthritic secretome. Int J Mol Sci 2013 Oct 15;14(10):20658-81.
          doi: 10.3390/ijms141020658pubmed: 24132152google scholar: lookup
        3. Deng M, Tang C, Yin L, Jiang Y, Huang Y, Feng Y, Chen C. Clinical and omics biomarkers in osteoarthritis diagnosis and treatment. J Orthop Translat 2025 Jan;50:295-305.
          doi: 10.1016/j.jot.2024.12.007pubmed: 39911590google scholar: lookup