The objective of this project is to elucidate the pathophysiological mechanisms for tendinitis using a novel in vitro model and an animal model. The central working hypothesis in this project is that tendon fibroblasts are responsible for the development of tendinitis by producing PGE2, which is upregulated by increased expression levels of PLA2, COX-1 and COX-2, and that high levels of PGE2 cause dysfunction of the tendon fibroblasts, thus resulting in pathophysiological changes in tendons.
The specific aims of this project are: 1) to investigate the role of PLA2 and COX expression in the production of PGE2 by human tendon fibroblasts under repetitive mechanical stretching using a novel in vitro model; 2) to investigate the role of stretching-induced PGE2 in inflammatory gene expression, proliferation and collagen synthesis of the human tendon fibroblasts using a novel in vitro model; and 3) to determine the effect of repeated exposure of the patellar tendon to PGE2 on its biological, biochemical, and biomechanical properties in a rabbit model. To accomplish these aims, a multidisciplinary approach based on mechano-biology, molecular biology and biomechanics will be used.When completed, this project will provide insights into the pathophysiological mechanisms for tendinitis at the cellular and molecular levels. It will also provide clinically valuable data about the effect of repetitive inflammation due to PGE2 on the tendon structure and function, which will help develop strategies to prevent and treat tendinitis effectively. The findings from this study will also be useful in helping design experiments to study other repetitive motion disorders (e.g., carpal tunnel syndrome).
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