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Title: Crush injury in zebrafish tail as a model for human bone fracture repair
Author: Tomecka, Monika Jagoda
ISNI:       0000 0004 6060 480X
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2016
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Bone fracture injuries, as well as their consequences, are important clinical issues. Several questions raised about them cannot be answered from observations of patients, therefore animal models of human fractures are needed. Zebrafish crush injury was developed here as an accurate model for human bone fracture repair. Whilst studies of amputation of the zebrafish adult tail attracted much interest as a model for regeneration, there has been very limited analysis of the process of repair of bone fractures. To address this, I established a zebrafish crush model and characterized it in comparison to mammalian bone fracture models. I further evaluated its usage in the zebrafish bone mutant, frf, known model for Osteogenesis Imperfecta. I showed striking similarities in the way of fracture repair between frf, rodent OI models and humans. I tested common human bone disease drugs on the zebrafish crush healing, further showing the usefulness and relevance of the model. Upon treatment with Bisphosphonates, human OI drugs, I observed a significant reduction in the remodelling stage of fracture healing, as well as in spontaneous fracture formation in juvenile OI zebrafish. These results mimic human clinical data. Last, but not least, I introduced controlled S. aureus infections to the crush site in order to model human S. aureus fracture infections. In conclusion, I established zebrafish crush model relevant to human physiology and pathology. I proved its usefulness in bone fracture healing characterization studies, in determining bone pathogenicity as well as in bone related drug treatment efficiency, and infection disturbance in bone repair.
Supervisor: Roehl, Henry ; Carney, Tom Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available