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Home / Equine Research Bank / Equine Vet J / Matrix metalloproteinase-2 and -9 are activated in joint dis...
Equine veterinary journal1999; 31(4); 324-330; doi: 10.1111/j.2042-3306.1999.tb03825.x

Matrix metalloproteinase-2 and -9 are activated in joint diseases.

Abstract: A study was performed to identify the activation status of the gelatinase MMPs, MMP-2 and -9, in both normal and diseased equine articular tissues. In addition, the production and activation status of equine MMP-2 and -9 by equine articular cells and tissues in response to increasing IL-1beta concentrations was assessed. The study was performed to test the hypothesis that activation of MMPs is a fundamental step in the pathogenesis of joint diseases; and that this activation is mediated by the cytokine IL-1. Using purified equine MMP-2 and -9, the molecular weights of the zymogen and activated form of equine MMP-2 and -9 were identified by a combination of gelatin zymography and a gelatin degradation assay using aminophenylmercuric acetate as a chemical activator of the molecules. Normal equine articular tissues (cartilage and synovial membrane) maintained in short-term tissue culture produced MMP-2 zymogen alone, while similar tissues obtained from a variety of pathological conditions produce both zymogen and active MMP-2, as well as MMP-9 monomer and dimer. Activated MMP-9 was an inconsistent finding. Normal equine synovial fibroblasts in monolayer culture produced zymogen MMP-2 alone under basal conditions. A mild increase in active and zymogen MMP-2 levels occurred with IL-1beta treatment. Equine synovial membrane explants demonstrated a dose-dependent increase in active and zymogen MMP-2 and MMP-9 levels following IL-1beta treatment. Monolayer chondrocyte cell cultures demonstrated a dose-dependent mild increase in active and zymogen MMP-2 following IL-1beta treatment. Explant cartilage cultures demonstrated a dose-dependent mild increase in zymogen MMP-2 alone following IL-1beta treatment. This study supports the hypothesis that activation of MMPs is occurring in joint disease, and that in vitro stimulation of equine articular cells and tissues causes not only an increase in MMP production, but also an increase in amount of activated enzyme released. Further research is required to investigate the role of MMP activation in joint diseases, and to investigate the potential use of therapeutic agents, which inhibit MMP activation, in the treatment and prevention of joint diseases.
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Publication Date: 1999-08-24 PubMed ID: 10454092DOI: 10.1111/j.2042-3306.1999.tb03825.xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

The research article talks about a study conducted to examine the levels and activation of enzymes MMP-2 and MMP-9 in healthy and diseased horse joints, and the influence of IL-1beta concentrations on these enzymes. The idea was to verify if activation of these enzymes plays a key role in development of joint diseases.

Study on Gelatinase MMPs

  • The key subjects of this study were Matrix Metalloproteinases (MMPs -2 and -9), which are enzymes capable of breaking down extracellular matrix. Specifically, the researchers wanted to understand their activation status in healthy and diseased horse joint tissues.
  • The study also sought to understand how the levels and activation status of the enzymes reacted to increasing levels of IL-1beta, a pro-inflammatory cytokine believed to influence the activity of these enzymes.

Test Hypothesis

  • The hypothesis wasn’t vague; it proposed that activation of MMPs is a fundamental stage in the development of joint diseases. The hypothesis further suggested that this activation is probably triggered by the cytokine IL-1.

Key Findings of the Research

  • Chemistry work and experimentation allowed determining the molecular weights of the dormant and active versions of MMP -2 and -9.
  • Experimentation revealed that normal equine joint tissues produced only inactive MMP-2, while joint tissues from diseased joints produced both inactive and activated MMP-2 along with the MMP-9 enzyme in both its single and double forms. However, activated MMP-9 was found inconsistently.
  • Different samples of tissue and isolated cells reacted differently to IL-1beta treatment. The most consistent finding was a mild increase in both inactive and active forms of MMP-2. Notably, tissues and cells from the synovial membrane and chondrocyte cell cultures demonstrated a dose-dependent increase in the levels of MMP-2 and MMP-9.

Results of the Study

  • This research supports the original hypothesis that the activation of MMPs is occurring in joint disease. Not only there was an increase in MMP production on exposure to IL-1beta, but there was also an increase in the amount of activated enzyme released.
  • This study forms the basis for more detailed research into the role of MMP activation in joint diseases. With these findings, potential therapeutic agents that inhibit MMP activation may be explored for the treatment and prevention of joint diseases.

Cite This Article

APA
Clegg PD, Carter SD. (1999). Matrix metalloproteinase-2 and -9 are activated in joint diseases. Equine Vet J, 31(4), 324-330. https://doi.org/10.1111/j.2042-3306.1999.tb03825.x

Publication

Equine veterinary journal
ISSN: 0425-1644
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 31
Issue: 4
Pages: 324-330

Researcher Affiliations

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

    MeSH Terms

    • Animals
    • Cartilage, Articular / cytology
    • Cartilage, Articular / enzymology
    • Cells, Cultured
    • Chondrocytes / enzymology
    • Culture Techniques
    • Dose-Response Relationship, Drug
    • Enzyme Activation
    • Enzyme Precursors / analysis
    • Enzyme-Linked Immunosorbent Assay / veterinary
    • Fibroblasts / enzymology
    • Horse Diseases / enzymology
    • Horses
    • Interleukin-1 / pharmacology
    • Interleukin-1 / physiology
    • Joint Diseases / enzymology
    • Joint Diseases / veterinary
    • Matrix Metalloproteinase 2 / metabolism
    • Matrix Metalloproteinase 9 / metabolism
    • Osteoarthritis / enzymology
    • Osteoarthritis / veterinary
    • Osteochondritis Dissecans / enzymology
    • Osteochondritis Dissecans / veterinary
    • Recombinant Proteins / pharmacology
    • Synovial Membrane / cytology
    • Synovial Membrane / enzymology
    • Tibial Fractures / enzymology
    • Tibial Fractures / veterinary

    Citations

    This article has been cited 6 times.
    1. Zhou J, Gao X, Liu X, Yang S, Wei Z, Gong Y. Identification of target genes of Astragalus mongholicus and Saposhnikovia divaricata extracts in human synoviocytes for potential osteoarthritis treatment. Hereditas 2025 Oct 8;162(1):203.
      doi: 10.1186/s41065-025-00581-7pubmed: 41063226google scholar: lookup
    2. Euppayo T, Siengdee P, Limlenglert P, Nganvongpanit K, Watanabe G, Kasashima Y, Arai K. In vitro model of equine cartilage degradation; using cartilage pellets differentiated from bone marrow-derived mesenchymal stem cells. In Vitro Cell Dev Biol Anim 2025 Jun;61(6):694-702.
      doi: 10.1007/s11626-025-01049-8pubmed: 40425901google scholar: lookup
    3. Lin J, Huang Y, Lin X, Liu W, Wu X, Qiu H, Wang R. Bauhinia championii alleviates extracellular matrix degradation in IL-1β induced chondrocytes via miRNA-145-5p/TLR4/NF-κB axis. Heliyon 2023 Aug;9(8):e19138.
      doi: 10.1016/j.heliyon.2023.e19138pubmed: 37664703google scholar: lookup
    4. Chen YT, Hou CH, Hou SM, Liu JF. The effects of amphiregulin induced MMP-13 production in human osteoarthritis synovial fibroblast. Mediators Inflamm 2014;2014:759028.
      doi: 10.1155/2014/759028pubmed: 25147440google scholar: lookup
    5. Knott L, Avery NC, Hollander AP, Tarlton JF. Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a naturally occurring model of disease. Osteoarthritis Cartilage 2011 Sep;19(9):1150-7.
      doi: 10.1016/j.joca.2011.06.005pubmed: 21723952google scholar: lookup
    6. Rowan AD, Hui W, Cawston TE, Richards CD. Adenoviral gene transfer of interleukin-1 in combination with oncostatin M induces significant joint damage in a murine model. Am J Pathol 2003 Jun;162(6):1975-84.
      doi: 10.1016/S0002-9440(10)64330-1pubmed: 12759253google scholar: lookup
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