Novel models of tendon injury and gap junction modulation in tendon cell and tissue repair : a dissertation presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Massey University, Turitea, Manawatu, New Zealand

Abstract

Injuries of energy-storing tendons such as the equine superficial digital flexor tendon and the human Achilles tendon are responsible for significant health and financial costs. A good model of acute tendinopathy of energy-storing tendons is required to better understand the changes that occur within the injured tendon and thereby to aid in the development of successful treatment regimens. Connexin43 plays an important role in wound healing and is involved with the spread of cell death signals following injury. Understanding the effect of Connexin43 modulation on tendon injury could improve tendon healing rate and quality. Models of acute injury were developed in the pelvic limb superficial digital flexor tendon of sheep and adapted for the thoracic limb superficial digital flexor tendon in horses. The sheep injury model was used to investigate the effects of injury on Connexin43 expression and the effect of Connexin43 antisense oligodeoxynucleotides in the peracute (2 to 4 hours) post injury stage. The model in horses was monitored clinically and ultrasonographically and these findings were related to the gross and histological changes at post mortem after 4 days. A surgical model of acute tendon injury was successfully developed and applied to sheep and horse energy-storing tendons. This has potential for modelling tendon injury in horses and humans. Increased Connexin43 levels were measured at the injury site at 2-4 hours post injury. Antisense oligodeoxynucleotides did not significantly reduce Connexin43 levels in the injured tendons in the acute period. Equine superficial digital flexor tendon-derived fibroblasts derived from different horses exhibit different cell growth rates that may be an indicator of a genetic ability to heal more effectively. The new models of acute tendon injury may facilitate development of an accurate model of clinical tendon injury in energy storing tendons to improve our knowledge of the problem and our treatments.