A role for intrinsic tendon cells in overuse injury

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中常见的挑战，导致慢性疼痛，功能残疾甚至肌腱断裂。大多数慢性肌腱损伤和疾病被认为是由反复暴露在显微镜下“损伤”组织的低强度力开始的。然而，重复性负荷（所谓的“过度使用”）在慢性肌腱损伤发病机制中的作用尚不清楚。特别是，肌腱病是在没有炎症的情况下发生退行性变化的一种情况。在这些情况下，推测疲劳肌腱失去了其内源性修复能力。重复性的微创伤可能会破坏肌腱细胞修复损伤的能力，甚至会刺激肌腱细胞以一种降解局部细胞外基质的方式做出反应。持续的重复活动可能导致损伤的累积，最终破坏肌腱的结构。

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.