New Imaging to Model the mechanical drivers of osteoarthritis

Andrew Pitsillides (primary)
Comparative Biomedical Sciences
Royal Veterinary College
David Abraham (secondary)
Inflammation
UCL

Abstract

Osteoarthritis has genetic and mechanical aetiology. Using our mouse joint loading model, which has revealed: i) magnitude-related lesion induction, and ii) progression, upon habitual use, the PhD will address the basis for the mechanical initiation of osteoarthritis and its progresses due solely to repetitive habitual loading. This PhD combines quasi-static loading, finite element analysis, Synchrotron and microCT imaging to model joint conditions, and computer-based replication to define mechanics. Specific gene contributions will be explored using mutant mice from ‘MRC bone network’. This multi-scale interdisciplinary approach will identify genetic and mechanical interplay in osteoarthritis.


References

1. Pitsillides AA and Beier F. (2011) Cartilage biology in osteoarthritis – lessons from developmental biology. Nature Reviews Rheumatology. 7(11), 654-663.

2. Poulet B, Hamilton RW, Shefelbine S and Pitsillides AA. (2011) Characterising a novel and adjustable non-invasive murine knee joint loading model. Arthritis & Rheumatism. 2011 63(1):137-47.

3. Staines KA, Poulet B, Wentworth DN, Pitsillides AA. (2016) The STR/ort mouse model of spontaneous osteoarthritis – an update. Osteoarthritis Cartilage. Dec 11. pii: S1063-4584(16)30478-2.

4. Javaheri B, Hopkinson M, Poulet B, Pollard AS, Shefelbine SJ, Chang Y, Francis-West P, Bou-Gharios G, Pitsillides AA. (2016) Deficiency and also transgenic overexpression of Timp-3 lead to compromised bone mass and architecture in vivo. PLoS ONE. 11(8):e0159657.

5. Staines KA, Madi K, Mirczuk SM, Parker S, Burleigh A, Poulet B, Hopkinson M, Bodey AJ, Fowkes RC, Farquharson C, Lee PD, Pitsillides AA. (2016) Endochondral growth defect and deployment of transient chondrocyte behaviours underlie osteoarthritis onset in a natural murine model. Arthritis and Rheumatism. 68(4):880-91. doi: 10.1002/art.39508.


BBSRC Area
Animal disease, health and welfareGenes, development and STEM* approaches to biology
Area of Biology
AgeingCell Biology
Techniques & Approaches
BiochemistryBioinformaticsEngineeringImage ProcessingMicroscopy / ElectrophysiologySimulation / Modelling