Format

Send to

Choose Destination
Dis Model Mech. 2019 Sep 3;12(9). pii: dmm037630. doi: 10.1242/dmm.037630.

Clinical pathologies of bone fracture modelled in zebrafish.

Author information

1
Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Proteos, 138673, Singapore.
2
Department of Biomedical Science, Firth Court, Western Bank, The University of Sheffield, Sheffield, S10 2TN, United Kingdom.
3
Lee Kong Chian School of Medicine, Experimental Medicine Building, Yunnan Garden Campus, 59 Nanyang Drive, Nanyang Technological University 636921, Singapore.
4
Department of Biomedical Science, Firth Court, Western Bank, The University of Sheffield, Sheffield, S10 2TN, United Kingdom h.roehl@sheffield.ac.uk tcarney@ntu.edu.sg.
5
Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Proteos, 138673, Singapore h.roehl@sheffield.ac.uk tcarney@ntu.edu.sg.

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.

KEYWORDS:

Bisphosphonate; Bone; Callus; Fracture; Osteogenesis imperfecta; Staphylococcus aureus; Zebrafish

PMID:
31383797
DOI:
10.1242/dmm.037630
Free PMC Article

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center