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Scientific reports2021; 11(1); 12451; doi: 10.1038/s41598-021-91914-9

Species variations in tenocytes’ response to inflammation require careful selection of animal models for tendon research.

Abstract: For research on tendon injury, many different animal models are utilized; however, the extent to which these species simulate the clinical condition and disease pathophysiology has not yet been critically evaluated. Considering the importance of inflammation in tendon disease, this study compared the cellular and molecular features of inflammation in tenocytes of humans and four common model species (mouse, rat, sheep, and horse). While mouse and rat tenocytes most closely equalled human tenocytes' low proliferation capacity and the negligible effect of inflammation on proliferation, the wound closure speed of humans was best approximated by rats and horses. The overall gene expression of human tenocytes was most similar to mice under healthy, to horses under transient and to sheep under constant inflammatory conditions. Humans were best matched by mice and horses in their tendon marker and collagen expression, by horses in extracellular matrix remodelling genes, and by rats in inflammatory mediators. As no single animal model perfectly replicates the clinical condition and sufficiently emulates human tenocytes, fit-for-purpose selection of the model species for each specific research question and combination of data from multiple species will be essential to optimize translational predictive validity.
Publication Date: 2021-06-14 PubMed ID: 34127759PubMed Central: PMC8203623DOI: 10.1038/s41598-021-91914-9Google Scholar: Lookup
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  • Journal Article
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  • Non-U.S. Gov't

Summary

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The research article discusses how various animal models represent different responses to tendon inflammation and emphasizes the need for careful selection of these models for tendon research.

Focus of the Research

  • The study aims to assess the similarity between human tendon cells (tenocytes) and those of different animals (mouse, rat, sheep, and horse) in terms of their responses to inflammation—a critical aspect of tendon diseases.

Finding Similarities and Differences Across Species

  • The researchers compared the tenocytes of humans and the four animals based on several parameters such as proliferation capacity, effect of inflammation on proliferation, speed of wound closure, and gene expression under healthy and inflammatory conditions.
  • It was found that mouse and rat tenocytes most closely matched the low proliferation capacity of human cells and the minimal effect inflammation has on this aspect.
  • In terms of wound healing rate, rats and horses were seen to mirror humans more closely.
  • The gene expression in human tenocytes was closest to that of mice under healthy conditions, horses under transient inflammation, and sheep under constant inflammation.

Other Comparisons and Observations

  • Markers that denote tendon characteristics (tendon marker and collagen) were most similarly expressed by mice and horses to humans.
  • When studying the genes associated with remodeling of the extracellular matrix (which can influence tissue structure and physiological properties), horses provided the best match.
  • Rats best resembled humans when it came to the expression of inflammatory mediators—substances that can modify or control inflammatory reactions.

Conclusions and Suggestions

  • The study concluded that no single animal model perfectly represents the clinical condition in humans or exhibits identical behavior to human tenocytes.
  • Thus, researchers are advised to choose their model species judiciously based on the specific requirements of their study.
  • The authors also suggest combining data from multiple species to maximize translational predictive validity—the ability to apply or translate the research data into practical clinical applications.

Cite This Article

APA
Oreff GL, Fenu M, Vogl C, Ribitsch I, Jenner F. (2021). Species variations in tenocytes’ response to inflammation require careful selection of animal models for tendon research. Sci Rep, 11(1), 12451. https://doi.org/10.1038/s41598-021-91914-9

Publication

ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 11
Issue: 1
Pages: 12451

Researcher Affiliations

Oreff, Gil Lola
  • Department of Companion Animals and Horses, Equine Surgery Unit, University of Veterinary Medicine Vienna, VETERM, Veterinaerplatz 1, 1210, Vienna, Austria.
Fenu, Michele
  • Department of Companion Animals and Horses, Equine Surgery Unit, University of Veterinary Medicine Vienna, VETERM, Veterinaerplatz 1, 1210, Vienna, Austria.
Vogl, Claus
  • Department of Biomedical Sciences, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210, Vienna, Austria.
Ribitsch, Iris
  • Department of Companion Animals and Horses, Equine Surgery Unit, University of Veterinary Medicine Vienna, VETERM, Veterinaerplatz 1, 1210, Vienna, Austria.
Jenner, Florien
  • Department of Companion Animals and Horses, Equine Surgery Unit, University of Veterinary Medicine Vienna, VETERM, Veterinaerplatz 1, 1210, Vienna, Austria. Florien.Jenner@vetmeduni.ac.at.

MeSH Terms

  • Animals
  • Cells, Cultured
  • Collagen / metabolism
  • Disease Models, Animal
  • Extracellular Matrix / metabolism
  • Female
  • Horses
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology
  • Mice
  • Primary Cell Culture
  • Rats
  • Sheep
  • Species Specificity
  • Tendon Injuries / immunology
  • Tendon Injuries / pathology
  • Tendons / cytology
  • Tendons / immunology
  • Tendons / pathology
  • Tenocytes / immunology
  • Tenocytes / metabolism

Conflict of Interest Statement

The authors declare no competing interests.

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