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Journal of veterinary pharmacology and therapeutics1998; 21(5); 406-413; doi: 10.1046/j.1365-2885.1998.00157.x

The effect of drugs commonly used in the treatment of equine articular disorders on the activity of equine matrix metalloproteinase-2 and 9.

Abstract: Loss of articular cartilage, which is the most important pathological lesion occurring in osteoarthritis, has been shown to be enzymatically mediated. The matrix metalloproteinases (MMPs) are a group of enzymes which have been implicated in this degradation of articular cartilage matrix. The use of pharmacological agents to inhibit this catabolic process in the joint is a potential route for therapeutic intervention. The gelatinase MMPs, MMPs-2 and 9, were purified by affinity chromatography from equine cell cultures. The ability of phenylbutazone, flunixin, betamethasone, dexamethasone, methylprednisolone acetate (MPA), hyaluronan, pentosan polysulphate and polysulphated glycosaminoglycan (PSGAG) to inhibit equine MMPs-2 and 9 were assessed by two degradation assays. Whilst some agents did have direct effects on MMP activity, these effects were only obtained at concentrations which were unlikely to be achieved for any length of time in vivo. It is improbable that any pharmacological agent, currently used in the horse, has a significant effect on gelatinase MMP activity.
Publication Date: 1998-11-12 PubMed ID: 9811443DOI: 10.1046/j.1365-2885.1998.00157.xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research explores the impact of various drugs typically used in treating horse joint diseases on the activity of certain enzymes called Matrix Metalloproteinase-2 and 9. The study concludes that while some drugs may affect these enzymes, the concentration required for this effect is unlikely to be sustained in real-life circumstances.

Objective of the Research

  • The focus of the study lies in understanding if common pharmacological agents used in the treatment of equine articular disorders have any direct effect on the activity of two specific enzymes – matrix metalloproteinase-2 and 9 (MMPs-2 and 9).

Background

  • The deterioration of articular cartilage – a key pathological symptom in osteoarthritis – is believed to be facilitated by certain enzymes. One group of these enzymes, known as the matrix metalloproteinases (MMPs), are thought to be responsible for the degradation of articular cartilage matrix.
  • MMP-2 and MMP-9, in particular, are connected to the degradation process. Using drugs to inhibit the activity of these enzymes might potentially offer a therapeutic solution for dealing with articular disorders.

Methodology

  • The researchers used affinity chromatography to purify the specific MMPs from equine cell cultures.
  • They then tested the ability of various drugs – including phenylbutazone, flunixin, betamethasone, dexamethasone, and others – to inhibit the activity of the purified equine MMPs-2 and 9. This was done through two degradation assays.

Findings

  • The results indicated that while some drugs do have a direct effect on the activity of MMP-2 and MMP-9, the effect could only be obtained at concentrations unlikely to be sustainable in vivo – that is, in a living organism.

Conclusion

  • The study concludes that it’s unlikely for a pharmacological agent, currently used for treatment in horses, to have a significant impact on the activity of MMP-2 and MMP-9 enzymes. This suggests that new approaches may be needed to combat enzymatically mediated degradation of articular cartilage in horses.

Cite This Article

APA
Clegg PD, Jones MD, Carter SD. (1998). The effect of drugs commonly used in the treatment of equine articular disorders on the activity of equine matrix metalloproteinase-2 and 9. J Vet Pharmacol Ther, 21(5), 406-413. https://doi.org/10.1046/j.1365-2885.1998.00157.x

Publication

ISSN: 0140-7783
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 21
Issue: 5
Pages: 406-413

Researcher Affiliations

Clegg, P D
  • Department of Veterinary Clinical Science and Animal Husbandry, University Veterinary Teaching Hospital, University of Liverpool, Leahurst, Neston, UK.
Jones, M D
    Carter, S D

      MeSH Terms

      • Animals
      • Antirheumatic Agents / pharmacology
      • Cartilage, Articular / enzymology
      • Cartilage, Articular / metabolism
      • Cartilage, Articular / pathology
      • Collagenases / metabolism
      • Gelatinases / metabolism
      • Horse Diseases / drug therapy
      • Horse Diseases / enzymology
      • Horses / physiology
      • In Vitro Techniques
      • Matrix Metalloproteinase 2
      • Matrix Metalloproteinase 9
      • Metalloendopeptidases / metabolism
      • Osteoarthritis / drug therapy
      • Osteoarthritis / enzymology
      • Osteoarthritis / veterinary