Modulation du processus inflammatoire et réparation tendineuse
|Advisor:||Frenette, Jérôme; Côté, Claude H.|
|Abstract:||Tendinopathies show a high prevalence and can alter the quality of life for many years. Nevertheless, the pathophysiology of tendinopathies is not well characterized and it may explain the lack of effective treatments to accelerate tendon healing. This thesis was therefore dedicated to the study the role of potential regulators of the pathophysiological sequence following tendon trauma. In a first project we set up an experimental model of acute tendon injury where collagenase was injected into the Achilles tendon of rats. This procedure induces a classical sequence of accumulation of leukocytes where neutrophils accumulate massively 24 hours following the injection of collagenase, followed by macrophages on day 3. We also showed, in a second project, that injection of collagenase reduces the load to failure by more than 50% 3 days post trauma. Moreover, administration of diclofenac, a non-steroidal anti-inflammatory drug, did not rescue tendons from that loss of mechanical strength, presumably because the anti-inflammatory effect was located in the paratenon and not in the core of the tendon where the load-resisting collagen bundles are located. In a third project we studied the role of p53, a putative regulator of the inflammatory process and extracellular matrix homeostasis, on the pathophysiological sequence following an acute tendon trauma. Transactivation inhibition of p53 reduced the accumulation of neutrophils and macrophages in the entire tendon. This anti-inflammatory effect was not associated to a rescue of the mechanical properties and even delayed the onset of healing. In view of the evidence that anti-inflammatory strategies failed to rescue tendons from functional loss, we challenged the dogma that the inflammatory process could induce non-specific damages to the tendon extracellular matrix. Intra-tendinous injection of carrageenan induced a massive accumulation of inflammatory cells. However this was neither associated to a reduction of tendons’ collagen content nor to a reduction of the load to failure. In conclusion, we identified new mediators and mechanisms of the pathophysiology of tendons. Our results challenge the concept that inflammatory cells strictly play deleterious effects following tendon trauma.|
|Document Type:||Thèse de doctorat|
|Open Access Date:||12 April 2018|
|Collection:||Thèses et mémoires|
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