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dc.contributor.authorRowson, Daniel Thomas
dc.identifier.citationRowson, DT. 2018. Mechanical Regulation of Primary Cilia in Tendon. Queen Mary University of Londonen_US
dc.description.abstractDuring normal activity, tendons are subjected to dynamic tensile strains of approximately 1-10%, whilst mechanical overload can lead to damage and degradation and the development of tendinopathy. The tenocytes within tendon respond to this mechanical environment although the mechanisms are poorly understood. Primary cilia consist of a slender axoneme composed of acetylated α-tubulin and are known to regulate a variety of signalling pathways including mechanosignalling. In various cell types, mechanical loading also influences primary cilia length. However relatively little is known about tendon primary cilia structure and function. This thesis set out to examine the structure and organisation of primary cilia in tendon cells and the effect of mechanical loading, both in situ and in isolated cells cultured in monolayer. Studies analysed cilia expression using confocal immunofluorescence microscopy in tendon fascicles from rat tail and isolated human tenocytes. Results demonstrated that the prevalence and orientation of primary cilia was different in the fascicular matrix (FM) and interfascicular matrix (IFM) regions of the tendon. Stress deprivation caused differential cilia elongation between the FM and IFM, associated with disruption of the surrounding extracellular matrix and alterations in tissue biomechanics. In isolated tenocytes, primary cilia were significantly longer with a greater prevalence than in situ. Cyclic tensile loading applied using the Flexcell system resulted in cilia disassembly within 8 hours with a dramatic reduction in prevalence and length. This effect was completely reversible on removal of strain. A similar response was observed in situ within both FM and IFM regions of the tendon. This mechanically-induced cilia disassembly was shown to be mediated, at least in part, by the release of TGFβ and activation of HDAC6 which causes tubulin deacetylation. These results in this thesis suggest a novel feedback mechanism through which physiological and pathological mechanical loading may regulate primary cilia signalling.en_US
dc.publisherQueen Mary University of Londonen_US
dc.rightsThe 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
dc.subjectEngineering and Materials Scienceen_US
dc.subjectPrimary Ciliaen_US
dc.titleMechanical Regulation of Primary Cilia in Tendonen_US

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  • Theses [3709]
    Theses Awarded by Queen Mary University of London

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