A Multidisciplinary Study of Mechanisms for Tendinitis

描述：本项目的目的是利用一种新的体外模型和动物模型来阐明肌腱炎的病理生理机制。该项目的中心工作假设是，肌腱成纤维细胞通过产生PGE2而导致肌腱炎的发生，而PLA2、COX-1和COX-2的表达水平升高会上调PGE2的表达，而高水平的PGE2会导致肌腱成纤维细胞功能障碍，从而导致肌腱的病理生理变化。本项目的具体目标是：1)使用一种新的体外模型，研究PLA2和COX在重复机械拉伸下人腱成纤维细胞产生前列腺素E_2(PGE_2)中的作用；2)使用一种新的体外模型，研究拉伸诱导的PGE_2在人腱成纤维细胞炎症基因表达、增殖和胶原合成中的作用；以及(3)在兔模型中确定反复暴露于PGE_2对其生物、生化和生物力学特性的影响。为了实现这些目标，将使用基于机械生物学、分子生物学和生物力学的多学科方法。完成后，该项目将在细胞和分子水平上为肌腱炎的病理生理机制提供深入的见解。这也将为研究前列腺素E_2引起的反复炎症对肌腱结构和功能的影响提供有临床价值的数据，这将有助于制定有效预防和治疗肌腱炎的策略。这项研究的发现也将有助于设计实验来研究其他重复运动障碍(例如，腕管综合征)。

DESCRIPTION: 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).