• Login
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    Interactions between primary cilia length and hedgehog signalling in response to mechanical and thermal stress. 
    •   QMRO Home
    • Queen Mary University of London Theses
    • Theses
    • Interactions between primary cilia length and hedgehog signalling in response to mechanical and thermal stress.
    •   QMRO Home
    • Queen Mary University of London Theses
    • Theses
    • Interactions between primary cilia length and hedgehog signalling in response to mechanical and thermal stress.
    ‌
    ‌

    Browse

    All of QMROCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    ‌
    ‌

    Administrators only

    Login
    ‌
    ‌

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Interactions between primary cilia length and hedgehog signalling in response to mechanical and thermal stress.

    View/Open
    Thompson_Clare_PhD_final.pdf (13.57Mb)
    Publisher
    Queen Mary University of London
    Metadata
    Show full item record
    Abstract
    The primary cilium is a microtubule-based organelle present on the majority of interphase cells where it functions as a hub for numerous signalling pathways including hedgehog signalling. Chondrocytes, the unique cellular component of articular cartilage, possess primary cilia which are required for mechanotransduction and maintenance of a healthy extracellular matrix. However in osteoarthritis there is an increase in primary cilia length and prevalence associated with aberrant activation of hedgehog signalling which promotes cartilage degradation. The aim of this thesis was therefore to examine the influence of biophysical stimuli on chondrocyte primary cilia structure and function, relating changes in ciliary length to perturbations in hedgehog signalling. An in vitro mechanical loading model was established to study the influence of cyclic tensile strain on chondrocyte primary cilia. Loading at 10% strain activated hedgehog signalling measured by expression of Gli1 and Ptch1. Cilia progressively disassembled in response to increasing levels of mechanical strain in a manner dependent upon tubulin deacetylation. Cilia disassembly at 20% strain was associated with the loss of mechanosensitive hedgehog signalling despite continued expression of hedgehog ligand (Ihh). Therefore this behaviour may function as a protective mechanism limiting hedgehog-mediated cartilage degradation in response to high levels of mechanical strain. To further understand the influence the extracellular environment exerts over ciliary function, a second in vitro model was developed investigating the effects of thermal stress. In chondrocytes and fibroblasts, primary cilia underwent rapid resorption in response to elevated temperature and ligand mediated hedgehog signalling was inhibited. These studies demonstrate that regulated disassembly of the cilium in response to physical stress modulates both cilia size and function. In particular, the findings suggest that changes in the chondrocyte physical environment affect cilia structure and function and may therefore be an important factor in the aetiology of cartilage disease.
    Authors
    Thompson, Clare
    URI
    http://qmro.qmul.ac.uk/xmlui/handle/123456789/8720
    Collections
    • Theses [3321]
    Copyright statements
    The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author
    Twitter iconFollow QMUL on Twitter
    Twitter iconFollow QM Research
    Online on twitter
    Facebook iconLike us on Facebook
    • Site Map
    • Privacy and cookies
    • Disclaimer
    • Accessibility
    • Contacts
    • Intranet
    • Current students

    Modern Slavery Statement

    Queen Mary University of London
    Mile End Road
    London E1 4NS
    Tel: +44 (0)20 7882 5555

    © Queen Mary University of London.