Zebrafish jaw movement

Background: Osteoarthritis is the most common joint disease globally, with 8 million people suffering from this disease in the UK alone. Currently there is no cure: the only treatments available focus on pain relief and ultimately joint replacement. While we know that genetics and mechanical loading (through use of the joint) are the major risks for osteoarthritis we still don’t completely understand how either affects the cells of the joint in the early disease stages. Zebrafish develop rapidly, share most of their genes with people, and are translucent. This allows us to watch cells in the living fish organise to form the skeleton and test for changes in response to genes or loading.   Outline: Abaqus was used to model jaw movement in two genotypes of zebrafish: wild type ("normal") fish, and mutant fish that express a gene associated with severe and early onset osteoarthritis. The mutant fish have altered joint shape and material properties compared to the wild type fish. These models enabled us to investigate how these changes impacted on biomechanical performance through the jaw of larval zebrafish. Finite Element Analysis (FEA) in Abaqus showed that joint shape had a greater impact on the pattern of skeletal strain than material properties.   Experiment procedure: To make these models, confocal image stacks of the zebrafish lower jaw were segmented and meshed. The mesh was separated into regions corresponding to cells of different maturity so that specific material properties could be assigned to each region. Atomic Force Microscopy (AFM) was used to determine the material properties for each region in wild type and mutant fish, with the mutant jaw having stiffer tissue than the wild type. The mesh was modelled using tetrahedral elements and exported for Abaqus. Modelling: In Abaqus/CAE, displacement/rotation boundary conditions were created at three points on the jaw; one point held the model in space, and the other two points were constrained in two axes to simulate the normal range of motion. Two steps were created to simulate loading for jaw closing and jaw opening respectively. Jaw muscle forces were recreated in Abaqus using the datum tool. Muscle attachment points were correlated to node sets. Custom datum coordinate systems were created to simulate the direction of muscle force vectors. Concentrated force loads were based on muscle fibre mass readings. The modelled jaw closing/opening movement was validated against videos of live specimen jaw movement, and show the effectiveness of this modelling approach. For the first experiment, the jaws were compared for minimum and maximal principal strains and strain distribution after running the analysis. A second experiment was run where the material properties for each genotype of zebrafish were swapped around in Abaqus, such that the wild type shape was assigned mutant material properties and the mutant shape was assigned wild type material properties. This was to compare the effect of material properties against the different joint tissue architecture. The results were that joint shape had a larger impact on jaw movement and strains than material properties.   Next stages: Next, we will model zebrafish that have been exposed to different gravity levels. This has the aim of helping inform therapies for astronauts, since astronauts returning from space are also more at risk of developing osteoarthritis than the general population. This work is being performed in part for the Spin Your Thesis! programme run by the European Space Agency's Education Office, and the Hammond Lab at the University of Bristol. For more information on the project see our submitted paper and our Facebook team project page.