Clinical pathologies of bone fracture modelled in zebrafish

Disease Models & Mechanisms
Monika J TomeckaTom J Carney

Abstract

Reduced bone quality or mineral density predict susceptibility to fracture and also attenuate subsequent repair. Bone regrowth is also compromised by bacterial infection, which exacerbates fracture site inflammation. Because of the cellular complexity of fracture repair, as well as genetic and environmental influences, there is a need for models that permit visualisation of the fracture repair process under clinically relevant conditions. To characterise the process of fracture repair in zebrafish, we employed a crush fracture of fin rays, coupled with histological and transgenic labelling of cellular responses; the results demonstrate a strong similarity to the phased response in humans. We applied our analysis to a zebrafish model of osteogenesis imperfecta (OI), which shows reduced bone quality, spontaneous fractures and propensity for non-unions. We found deficiencies in the formation of a bone callus during fracture repair in our OI model and showed that clinically employed antiresorptive bisphosphonates can reduce spontaneous fractures in OI fish and also measurably reduce fracture callus remodelling in wild-type fish. The csf1ra mutant, which has reduced osteoclast numbers, also showed reduced callus remodelling. Exposur...Continue Reading

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Citations

Sep 12, 2020·Histochemistry and Cell Biology·Joanna J MossJon D Lane
Nov 28, 2019·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Björn BusseRonald Y Kwon
Dec 13, 2019·BioMed Research International·Marta CarnovaliMassimo Mariotti
Jan 24, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Kristin DietrichFranziska Knopf
May 5, 2021·The Journal of Cell Biology·Nicola L StevensonDavid J Stephens
Sep 8, 2021·Frontiers in Genetics·Manuel Marí-BeffaIvan Duran
Nov 6, 2021·Journal of Aquatic Animal Health·Emma L HouckJeffrey A Buckel

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Methods Mentioned

BETA
transgenic
dissection
PCR
light microscopy

Software Mentioned

GraphPad
ImageJ
Prism

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