Biology subjects

Aggleton, J. A.

Publications and source records attributed to Aggleton, J. A..

3 recordsLinked to original sources

bioRxiv2020

Exposure to hypergravity during development leads to altered cartilage material properties and strain distribution in zebrafish.

Terrestrial vertebrates have adapted to life on Earth and its constant gravitational field, which exerts load on the body and influences the structure and function of tissues. While the effects of microgravity on muscle and bone homeostasis are well described, the effects of shorter exposures to increased gravitational fields are less well characterized. Here, we exposed zebrafish to 3 and 6g hypergravity from 3-5 days post fertilisation, when key events in jaw cartilage morphogenesis occur. We did not observe changes to growth, or morphology of cartilage or muscle. However, we observed altered mechanical properties of jaw cartilages. We model the impact of these material property changes using Finite Element Analysis and show strain distribution in the jaw is altered following hypergravity. In regions of predicted altered strain we observed local changes to chondrocyte morphology, suggesting altered gravity affects chondrocyte maturation, ultimately leading to changes to cartilage structure and function.

physiology↗

bioRxiv2019

Finite Element and deformation analyses predict pattern of bone failure in loaded zebrafish spines

The spine is the central skeletal support structure in vertebrates consisting of repeated units of bone, the vertebrae, separated by intervertebral discs that enable the movement of the spine. Spinal pathologies such as idiopathic back pain, vertebral compression fractures and intervertebral disc failure affect millions of people world-wide. Animal models can help us to understand the disease process, and zebrafish are increasingly used as they are highly genetically tractable, their spines are axially loaded like humans, and they show similar pathologies to humans during ageing. However biomechanical models for the zebrafish are largely lacking. Here we describe the results of loading intact zebrafish spinal motion segments on a material testing stage within a micro Computed Tomography machine. We show that vertebrae and their arches show predictable patterns of deformation prior to their ultimate failure, in a pattern dependent on their position within the segment. We further show using geometric morphometrics which regions of the vertebra deform the most during loading, and that Finite Element models of the trunk subjected reflect the real patterns of deformation and strain seen during loading and can therefore be used as a predictive model for biomechanical performance.

physiology↗

bioRxiv2018

The mechanical impact of col11a2 loss on joints; col11a2 mutant zebrafish show changes to joint development and function which lead to early onset osteoarthritis

Abstract (max 200 words)Collagen is the major structural component of cartilage and mutations in the genes encoding Type XI collagen are associated with severe skeletal dysplasias (Fibrochondrogenesis and Stickler syndrome) and early onset osteoarthritis. The impact of the lack of Type XI collagen on cell behaviour and mechanical performance during skeleton development is unknown. We studied a zebrafish mutant for col11a2 and evaluated cartilage, bone development and mechanical properties to address this. We show that in col11a2 mutants Type II collagen is made but is prematurely degraded in maturing cartilage and ectopically expressed in the joint. These changes are correlated with increased stiffness of both bone and cartilage; quantified using Atomic Force Microscopy. In the mutants, the skeletal rudiment terminal region in the jaw joint are broader and the interzone smaller. These differences in shape and material properties impact on joint function and mechanical performance, which we modelled using Finite Element Analyses. Finally, we show that col11a2 heterozygous carriers reach adulthood but show signs of severe early onset osteoarthritis. Taken together our data demonstrate a key role for Type XI collagen in maintaining the properties of cartilage matrix; which when lost leads to alterations to cell behaviour that give rise to joint pathologies.

developmental biology↗