TY - JOUR T1 - Species variations in tenocytes’ response to inflammation require careful selection of animal models for tendon research JF - bioRxiv DO - 10.1101/2021.05.09.443263 SP - 2021.05.09.443263 AU - Gil Lola Oreff AU - Michele Fenu AU - Claus Vogl AU - Iris Ribitsch AU - Florien Jenner Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/10/2021.05.09.443263.abstract N2 - 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.Competing Interest StatementThe authors have declared no competing interest. ER -