A role for intrinsic tendon cells in overuse injury

内在肌腱细胞在过度使用损伤中的作用

• 批准号: 6708370
• 负责人: Kathleen Anne Derwin
• 金额: $ 7.65万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6708370
• 关键词: SDS polyacrylamide gel electrophoresis; animal tissue; cell death; cell morphology; chronic disease /disorder; densitometry; enzyme activity; inflammation; mechanical stress; metalloendopeptidases; pathologic process; repetitive motion injury; tendon injury; terminal nick end labeling; tissue inhibitor of metalloproteinases; viscosity; western blottings

DESCRIPTION (provided by applicant): Overuse injuries and other tendon disorders represent a common challenge in orthopaedic medicine, resulting in chronic pain, functional disability and even tendon rupture. Most chronic tendon injuries and disorders are believed to start from repeated exposure to low-magnitude forces that 'injure' the tissue microscopically. However, the role of repetitive loading-- so-called 'overuse'-- in the pathogenesis of chronic tendon injury is not well-understood. In particular, tendinosis is a condition where degenerative changes occur in the absence of inflammation. In these cases it is speculated that fatigued tendon loses its endogenous reparative ability. Repetitive microtrauma may overwhelm the ability of tendon cells to repair damage, or even incite them to respond in a manner that is degradative to their local extracellular matrix. Continued repetitive activity may lead to an accumulation of damage that eventually disrupts the structure of the tendon. Because chronic tendon injuries are believed to start from repeated exposure to low-magnitude forces, we hypothesize that they are the result of cell-mediated processes (e.g., aberrant repair and/or directed degradation) rather than material fatigue. We will explore this hypothesis in an organ culture model where tendon cells can be maintained in their native three-dimensional environment. To differentiate between damage that is cell-mediated and damage due to material fatigue alone, we will first establish and then cyclically load a devitalized tendon explant to assess material damage. We will then investigate if cyclic mechanical load will instigate a damage response in vital tendon explants and whether the loads are less than those required to acutely damage devitalized tendon. A role for intrinsic tendon cells in the pathogenesis of tendon overuse injury would be implied by a lower damage threshold in vital tendon.

描述（由申请人提供）：过度使用损伤和其他肌腱疾病是骨科医学的常见挑战，导致慢性疼痛、功能障碍甚至肌腱断裂。 大多数慢性肌腱损伤和疾病被认为是从反复暴露于微观上“损伤”组织的低强度力开始的。 然而，重复负荷-所谓的“过度使用”-在慢性肌腱损伤的发病机制中的作用还没有得到很好的理解。特别是，肌腱病是一种在没有炎症的情况下发生退行性变化的病症。 在这些情况下，据推测，疲劳肌腱失去其内源性修复能力。 重复性微创伤可能会压倒肌腱细胞修复损伤的能力，甚至会刺激它们以降解其局部细胞外基质的方式做出反应。 持续的重复性活动可能导致损伤的累积，最终破坏肌腱的结构。 由于慢性肌腱损伤被认为是从反复暴露于低强度的力开始的，我们假设它们是细胞介导过程的结果（例如，异常修复和/或定向降解）而不是材料疲劳。我们将在器官培养模型中探索这一假设，在该模型中，肌腱细胞可以保持在其天然的三维环境中。 为了区分细胞介导的损伤和仅由材料疲劳引起的损伤，我们将首先建立并循环加载失活肌腱外植体以评估材料损伤。 然后，我们将研究循环机械载荷是否会在重要肌腱外植体中引发损伤反应，以及载荷是否小于急性损伤失活肌腱所需的载荷。 固有肌腱细胞在肌腱过度使用损伤的发病机制中的作用可能是由活腱较低的损伤阈值所暗示的。