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American journal of veterinary research2000; 61(6); 624-630; doi: 10.2460/ajvr.2000.61.624

Effects of interleukin-1beta and tumor necrosis factor-alpha on expression of matrix-related genes by cultured equine articular chondrocytes.

Abstract: To determine the effects of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) on expression and regulation of several matrix-related genes by equine articular chondrocytes. Methods: Articular cartilage harvested from grossly normal joints of 8 foals, 6 yearling horses, and 8 adult horses. Methods: Chondrocytes maintained in suspension cultures were treated with various doses of human recombinant IL-1beta or TNF-alpha. Northern blots of total RNA from untreated and treated chondrocytes were probed with equine complementary DNA (cDNA) probes for cartilage matrix-related genes. Incorporation of 35S-sulfate, fluorography of 14C-proline labeled medium, zymography, and western blotting were used to confirm effects on protein synthesis. Results: IL-1beta and TNF-alpha increased steady-state amounts of mRNA of matrix metalloproteinases 1, 3, and 13 by up to 100-fold. Amount of mRNA of tissue inhibitor of metalloproteinase-1 also increased but to a lesser extent (1.5- to 2-fold). Amounts of mRNA of type-II collagen and link protein were consistently decreased in a dose-dependent manner. Amount of aggrecan mRNA was decreased slightly; amounts of biglycan and decorin mRNA were minimally affected. Conclusions: Treatment of cultured equine chondrocytes with IL-1beta or TNF-alpha resulted in marked alterations in expression of various matrix and matrix-related genes consistent with the implicated involvement of these genes in arthritis. Expression of matrix metalloproteinases was increased far more than expression of their putative endogenous inhibitor. Results support the suggestion that IL-1beta and TNF-alpha play a role in the degradation of articular cartilage in arthritis.
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Publication Date: 2000-06-13 PubMed ID: 10850836DOI: 10.2460/ajvr.2000.61.624Google 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

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explored how interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), two biochemical agents, influence the expression of certain matrix-related genes in horse cartilage cells. The results showed that these agents considerably alter gene expression and could be involved in the progression of arthritis, as they potentially contribute to the degradation of joint cartilage.

Study Design and Methodology

The researchers conducted the experimental study on articular cartilage taken from healthy joints of eight foals, six yearling horses, and eight adult horses. Specifically, they:

  • Kept the chondrocytes (cartilage cells) in suspension cultures and treated them with varying doses of the biochemical agents IL-1beta or TNF-alpha.
  • Used Northern blots of the RNA taken from both untreated and treated chondrocytes, probing them with horse DNA sequences for cartilage matrix-related genes.
  • Verified the effects on protein synthesis using 35S-sulfate incorporation, fluorography of 14C-proline labeled medium, zymography, and western blotting techniques.

Key Findings

The results indicated that:

  • IL-1beta and TNF-alpha increased steady-state quantities of mRNA of matrix metalloproteinases (enzymes that break down proteins) 1, 3, and 13 by up to 100 times.
  • The mRNA amount of the tissue inhibitor of metalloproteinase-1, an agent that inhibits matrix metalloproteinases, increased as well, but only to a lesser extent (1.5- to 2-fold).
  • The mRNA amounts of type-II collagen and link protein consistently decreased in a dose-dependent manner.
  • The amount of aggrecan mRNA slightly declined, whereas the amounts of biglycan and decorin mRNA were minimally affected.

Conclusions and Implications

The treatment of horse chondrocytes with IL-1beta or TNF-alpha led to substantial alterations in the expression of various matrix and matrix-related genes. This aligns with the suspected involvement of these genes in arthritis progression, as the increase in matrix metalloproteinases was far higher than their supposed endogenous inhibitor. This suggests that IL-1beta and TNF-alpha potentially contribute to the degradation of articular cartilage in arthritis. These findings support the possibility of these agents being potential targets for therapeutic interventions in arthritis.

Cite This Article

APA
Richardson DW, Dodge GR. (2000). Effects of interleukin-1beta and tumor necrosis factor-alpha on expression of matrix-related genes by cultured equine articular chondrocytes. Am J Vet Res, 61(6), 624-630. https://doi.org/10.2460/ajvr.2000.61.624

Publication

American journal of veterinary research
ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 61
Issue: 6
Pages: 624-630

Researcher Affiliations

Richardson, D W
  • Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square 19348-1692, USA.
Dodge, G R

    MeSH Terms

    • Animals
    • Blotting, Northern / veterinary
    • Blotting, Western / veterinary
    • Cartilage, Articular / chemistry
    • Cartilage, Articular / cytology
    • Cartilage, Articular / physiology
    • Chondrocytes / chemistry
    • Chondrocytes / physiology
    • Collagenases / genetics
    • Collagenases / physiology
    • Electrophoresis, Polyacrylamide Gel / veterinary
    • Fluorometry / veterinary
    • Gene Expression Regulation, Enzymologic
    • Glycosaminoglycans / analysis
    • Horses / genetics
    • Horses / physiology
    • Image Processing, Computer-Assisted
    • Interleukin-1 / genetics
    • Interleukin-1 / physiology
    • Matrix Metalloproteinase 1 / genetics
    • Matrix Metalloproteinase 1 / physiology
    • Matrix Metalloproteinase 13
    • Matrix Metalloproteinase 3 / genetics
    • Matrix Metalloproteinase 3 / physiology
    • Matrix Metalloproteinases / genetics
    • Matrix Metalloproteinases / metabolism
    • Scintillation Counting
    • Statistics, Nonparametric
    • Sulfates / chemistry
    • Tumor Necrosis Factor-alpha / genetics
    • Tumor Necrosis Factor-alpha / physiology

    Grant Funding

    • AR42417 / NIAMS NIH HHS

    Citations

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