Insights into tendon damage from a diabetic rat model

Tendinopathy is one of the most common musculoskeletal injuries in humans (Walden et al., 2017). It is also, due to the essential role that tendons play in everyday movement and locomotion, one of the most impactful. The need to prevent, mitigate and treat its occurrence is thus clear although, in order for this possibility to exist, greater insight is first needed into the mechanistic causes of tendon damage and the structural responses to it. While it is known that repeated overloading and, alternatively, fatigue loading of a tendon will increase its susceptibility to damage there are a number of other factors that can prove influential. One of these is diabetes - a disease that is correlated with an increased incidence of tendinopathy (Abate et al., 2013) and can be considered as equivalent to an increase in age (Monnier et al., 1984) - which is often investigated experimentally via animal models. The mechanism behind the effect that diabetes has on tendon is thought to be advanced glycation end-product (AGE) presence, an increase in which can occur in both diabetic and older patients (Thorpe et al., 2010; Eriksen et al., 2014). Another factor is the functional role of the tendon in question: those that are involved in locomotion or are loaded heavily in vivo behave in a spring-like manner - with the ability to store and then release energy - while those that are positional′andusedforf∈e-mo→rcontroldo¬.In⊥hcasesthese∝ertiesaidtheperformanceoftherespectivefunctionsandthetendonshavestructurald⇔erencesassociatedwiththese(Keretal.,2000).Theaimofthisdissertationwasthus→exploretendondama≥-itsmechanismsandmarkers-andthemethodof∈vestigation∈cludedusingrattendonsom⊥hamodelofdiabetes(STZ') and from healthy controls with energy-storage and positional functional roles both being considered (tail tendons and Achilles tendons, respectively). Following a literature review (which, among other things, explored the definition of dama≥′andhowitismodel≤d)twod⇔erentmechanicaltestswereperformed:staticfatiguetest∈gandinterrupted' static fatigue testing. The first of these enabled the measurement of phenomenological markers related to damage, including the `steady-state strain rate' (SSSR) which showed strong, significant differences with STZ treatment (p=0.000001 in tails and p=0.04 in Achilles tendon) and functional role (p=0.01 in STZ samples and p=0.0001 in controls). The second mechanical test allowed the relationship between SSSR and a generally-accepted marker of tendon damage - a decrease in loading modulus - to be established in tail tendons (p=0.24 in STZ samples and p=0.02 in controls). It was thus concluded that SSSR is indeed a quantification of tendon susceptibility to damage. Finally, spectrofluorimetry was performed on STZ-treated and control samples in order to measure AGE presence. This revealed no significant difference (p=0.15), leading to the conclusion that other factors related to STZ treatment must necessarily be occurring. Possibly, these include AGE-related stiffening of bonds within the tendon's non-collagenous matrix.

Keywords: Tendon damage
Fatigue damage
Mechanical testing
Streptozotocin
Tendinopathy
Advisor: Thompson, M