Tendon disorders are hugely burdensome to individuals, costly on a societal level, and are being compounded by the increasingly ageing population. These chronic and often disabling conditions are poorly understood and lacking in an effective long-term treatment. Recently, attempts to elucidate the underlying mechanisms of tendon diseases in order to improve their prognosis have arrived at a key hypothesis: it is posited that the various tendons found throughout the body have unique properties, unique responses to disease-causing stimuli, and in turn therefore, different responses to the therapies being applied. It is possible this is why individual therapies are simultaneously effective in specific patient groups, and disappointingly ineffective in others.
The theme of distinct tendon phenotypes is central to this thesis. This body of work explores the hypothesis that functionally distinct tendons respond differently to changes in their loading environment, first by assessing properties developed in vivo in response to a surgically-induced injury of an equine tendon, and then the properties of ovine tendons developed in response to their distinct in vivo functions. It continues by then developing and applying in vitro loading environments, where more precisely controlled loading is used to understand how tendons with highly energy-storing functions may differ from simply positional tendons, at rest and under various loading conditions. The scope of the results span multiple levels, from cells and tissues, to the functional mechanical properties of multiple tendons and disease phenotypes, in order to better understand how these influence each other. This broad approach helps to try and unify work which has previously been isolated by discipline, and more accurately contextualise previous and future work to better understand tendon phenotypes.
The key findings of this thesis are: A focal tendon injury in the horse's energy-storing superficial digital exor tendon disrupted healthy relationships (e.g. biomechanics-glycosaminoglycans), and caused widespread increases in chondroitin/dermatan sulfate glycosaminoglycan levels, which were partially responsible for the concomitant reductions in modulus and ultimate tensile strength. A subsequent study of three functionally distinct ovine tendon types showed higher biomechanical properties of the medial branch of the common digital extensor tendon, a positional tendon, when compared to its energy-storing counterparts, and distinct responses to stress-deprivation, with regards to loss of glycosaminoglycans and biomechanical properties. The underpinning gene expression and immunohistochemistry results suggest that despite broad similarities between the tendon types, differences also exist at baseline and in response to stress-deprivation. When cyclic loading ± compression loading were applied identically to those functionally distinct ovine tendons for 10 days, there was a convergence between the tendons in terms of gene expression and histological appearances, but not biochemical properties.
Together, these results show there are differences between tendon types in baseline phenotype and mechanical properties and their response to perturbations in normal loading environments.
By improving our understanding of the heterogeneity of tendons found throughout the body and their unique responses, this thesis takes a step along the pathway towards more targeted treatment and improved outcomes for tendon disorders.