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Veterinary journal (London, England : 1997)2011; 190(2); e54-e59; doi: 10.1016/j.tvjl.2011.02.026

Hypoxia and a hypoxia mimetic up-regulate matrix metalloproteinase 2 and 9 in equine laminar keratinocytes.

Abstract: The aim of this study was to determine if hypoxia and the hypoxia mimetic cobalt chloride regulate the activity of matrix metalloproteinase (MMP)-2 and -9 in cultures of equine hoof keratinocytes. These effects were assessed in primary cultures of laminar keratinocytes using gelatin zymography. Incubation of keratinocytes with cobalt chloride significantly increased the levels of active MMP-2 compared to untreated controls. Hypoxia significantly increased the expression of active MMP-2 and -9 in keratinocyte cultures. This up-regulation was observed after 6h and peaked at 24h. The study findings provide novel evidence of a potential link between hypoxia within the hoof and up-regulation of MMPs which may in turn result in damage to the lamellar basement membrane.
Publication Date: 2011-04-01 PubMed ID: 21459025DOI: 10.1016/j.tvjl.2011.02.026Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This study examines how a lack of oxygen (hypoxia) and a substance that mimics this condition (cobalt chloride) increase the activity of two specific proteins in horse hoof cells, potentially leading to damage to the hoof structure.

Research Objective

  • The goal of this study was to understand if hypoxia and cobalt chloride, a chemical that mimics hypoxia, affect the behavior of matrix metalloproteinase (MMP)-2 and -9 in cultured cells taken from horse hooves.

Methodology

  • Cells from horse hooves, specifically laminar keratinocytes, were cultured in a laboratory setting.
  • The cellular activity of MMP-2 and -9 was monitored using a technique known as gelatin zymography, which uses gelatin to visualize the activity of these proteins.
  • The experiment exposed the cells to cobalt chloride and observed the changes in the MMP-2 and -9 activity compared to control cells which weren’t treated with cobalt chloride.
  • Separately, the experiment also exposed the cells to hypoxic conditions and recorded the changes in the activity of the MMP-2 and -9 proteins.

Findings

  • The study found that treating keratinocytes with cobalt chloride significantly increased the active levels of MMP-2 in comparison to untreated cells.
  • Hypoxia, too, raised the expression of active MMP-2 and -9 in these horse hoof cells. The researchers observed the increase in protein activity after 6 hours of exposure, reaching peak levels at 24 hours.

Implications

  • The researchers suggest that their findings provide new proof of a potential link between hypoxia, up-regulation of MMPs, and damage to the hoof structure in horses. In other words, lack of oxygen within the hoof or substances mimicking this condition could increase the activity of damaging proteins and lead to structural damage.
  • These findings could pave the way for additional research on horse hoof health and could potentially inform therapeutic strategies to prevent or manage hoof damage.

Cite This Article

APA
Medina-Torres CE, Mason SL, Floyd RV, Harris PA, Mobasheri A. (2011). Hypoxia and a hypoxia mimetic up-regulate matrix metalloproteinase 2 and 9 in equine laminar keratinocytes. Vet J, 190(2), e54-e59. https://doi.org/10.1016/j.tvjl.2011.02.026

Publication

ISSN: 1532-2971
NlmUniqueID: 9706281
Country: England
Language: English
Volume: 190
Issue: 2
Pages: e54-e59

Researcher Affiliations

Medina-Torres, Carlos E
  • School of Veterinary Science, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZJ, UK.
Mason, Sarah L
  • School of Veterinary Science, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZJ, UK.
Floyd, Rachel V
  • School of Biomedical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 3BX, UK.
Harris, Pat A
  • Equine Studies Group, WALTHAM Centre for Pet Nutrition, Waltham-on-the-Wolds, Melton Mowbray, Leicestershire LE14 4RT, UK.
Mobasheri, Ali
  • School of Veterinary Science and Medicine, Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Leicestershire LE12 5RD, UK. Electronic address: ali.mobasheri@nottingham.ac.uk.

MeSH Terms

  • Animals
  • Biomimetics
  • Cell Hypoxia
  • Cells, Cultured
  • Cobalt / pharmacology
  • Foot Diseases / enzymology
  • Foot Diseases / etiology
  • Foot Diseases / veterinary
  • Hoof and Claw / drug effects
  • Hoof and Claw / enzymology
  • Horse Diseases / enzymology
  • Horse Diseases / etiology
  • Horses
  • Hypoxia / complications
  • Hypoxia / enzymology
  • Hypoxia / veterinary
  • Keratinocytes / drug effects
  • Keratinocytes / enzymology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Up-Regulation

Citations

This article has been cited 6 times.
  1. Lan X, Qi D, Ren H, Liu T, Shao H, Zhang J. Chicoric acid ameliorates LPS-induced inflammatory injury in bovine lamellar keratinocytes by modulating the TLR4/MAPK/NF-κB signaling pathway. Sci Rep 2023 Dec 11;13(1):21963.
    doi: 10.1038/s41598-023-49169-zpubmed: 38082032google scholar: lookup
  2. Vercelli C, Tursi M, Miretti S, Giusto G, Gandini M, Re G, Valle E. Effect of sugar metabolite methylglyoxal on equine lamellar explants: An ex vivo model of laminitis. PLoS One 2021;16(7):e0253840.
    doi: 10.1371/journal.pone.0253840pubmed: 34314429google scholar: lookup
  3. Patan-Zugaj B, Egerbacher M, Licka TF. Endotoxin-induced changes in expression of cyclooxygenase isoforms in the lamellar tissue of extracorporeally haemoperfused equine limbs. Anat Histol Embryol 2020 Sep;49(5):597-605.
    doi: 10.1111/ahe.12520pubmed: 31774594google scholar: lookup
  4. Baskerville CL, Chockalingham S, Harris PA, Bailey SR. The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor. PeerJ 2018;6:e5945.
    doi: 10.7717/peerj.5945pubmed: 30519508google scholar: lookup
  5. Burns TA, Dembek KA, Kamr A, Dooley SB, Dunbar LK, Aarnes TK, Bednarski LS, O'Brien C, Lakritz J, Byrum B, Wade A, Farmer R, Tan S, Toribio RE. Effect of Intravenous Administration of Cobalt Chloride to Horses on Clinical and Hemodynamic Variables. J Vet Intern Med 2018 Jan;32(1):441-449.
    doi: 10.1111/jvim.15029pubmed: 29286554google scholar: lookup
  6. Reisinger N, Schaumberger S, Nagl V, Hessenberger S, Schatzmayr G. Concentration Dependent Influence of Lipopolysaccharides on Separation of Hoof Explants and Supernatant Lactic Acid Concentration in an Ex Vivo/In Vitro Laminitis Model. PLoS One 2015;10(11):e0143754.
    doi: 10.1371/journal.pone.0143754pubmed: 26599864google scholar: lookup