Bone fractures caused by overloading are common in racing Thoroughbreds and are the most common reason for euthanasia on the racecourse. Fracture risk is affected by environmental and genetic factors.

Challenge

Horse iPSCs can form a mineralised bone matrix (green) on a scaffold

Bone fractures are a significant welfare problem in the Thoroughbred racing industry. Previous work has demonstrated that fracture is a complex condition with both environmental and genetic factors risk factors. However, the specific genetic factors that underpin fracture risk have not been identified. This has proved problematic to work out using patients due to the difficulty in accessing bone tissue and the large variability in exposure to environmental risk factors.

Solution

It is now possible to use genome wide information to calculate an individual horse’s relative risk of fracture. Using this approach we have derived induced pluripotent stem cells (iPSCs) from horses at high and low genetic risk of fracture. iPSCs can grow forever in the laboratory and can turn into every cell type of the body. We have established protocols to turn equine iPSCs into the cells which make bone.  This provides us with a unique laboratory tool to study bone from high and low risk horses in the absence of any environmental variability.

Impact

Horse iPSCs growing in the laboratory

Identification of the genetic factors that underpin fracture risk in Thoroughbreds, and an understanding of the biological pathways that they affect, would provide a significant step forward to identify and manage high risk horses. Diagnostic imaging techniques to monitor horses for pre-fracture changes already exist but are prohibitively expensive to employ on a widescale. The ability to identify genetically high risk horses would enable the more targeted use of these methods.  

Furthermore, identifying the mechanisms which underpin genetic risk in horses will allow future research to develop novel therapies and interventions for high risk horses to decrease their risk of catastrophic facture. Identifying horses at high genetic risk would also allow breeders to make informed breeding decisions to reduce the probability of breeding horses at high genetic risk of fracture. This project therefore has the potential to significantly improve the health and welfare of racing Thoroughbreds.

Partners

We thank the Horserace Betting Levy Board (vet/prj/792)  and the Alborada Trust for funding this work.

Publications

Title Publication Year
Biocompatible 3D printed thermoplastic scaffolds for osteoblast differentiation of equine iPS cells Tissue Eng Part C Methods 2019
Osteoblast differentiation of equine induced pluripotent stem cells Biology Open 2018
Characterisation of companion animal pluripotent stem cells Cytometry A 2018
Equine Induced Pluripotent Stem Cells have a Reduced Tendon Differentiation Capacity Compared to Embryonic Stem Cells  Frontiers in Veterinary Science 2015

 

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