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Title: Clinical pathologies of bone fracture modelled in zebrafish
Authors: Tomecka, Monika J.
Ethiraj, Lalith P.
Sánchez, Luis M.
Roehl, Henry Hamilton
Carney, Tom J.
Keywords: Science::Medicine
Issue Date: 2019
Source: Tomecka, M. J., Ethiraj, L. P., Sánchez, L. M., Roehl, H. H., & Carney, T. J. (2019). Clinical pathologies of bone fracture modelled in zebrafish. Disease Models & Mechanisms, 12(9), dmm037630-. doi:10.1242/dmm.037630
Journal: Disease Models & Mechanisms
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. Exposure to excessive bisphosphonate, however, disrupted callus repair. Intriguingly, neutrophils initially colonised the fracture site, but were later completely excluded. However, when fractures were infected with Staphylococcus aureus, neutrophils were retained and compromised repair. This work elevates the zebrafish bone fracture model and indicates its utility in assessing conditions of relevance to an orthopaedic setting with medium throughput.This article has an associated First Person interview with the first author of the paper.
ISSN: 1754-8403
DOI: 10.1242/dmm.037630
Rights: © 2019 The Authors (published by The Company of Biologists Ltd). This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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