|dc.contributor.author||Rowson, Daniel Thomas||
|dc.identifier.citation||Rowson, DT. 2018. Mechanical Regulation of Primary Cilia in Tendon. Queen Mary University of London||en_US
|dc.description.abstract||During 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
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.publisher||Queen Mary University of London||en_US
|dc.rights||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||
|dc.subject||Engineering and Materials Science||en_US
|dc.title||Mechanical Regulation of Primary Cilia in Tendon||en_US