Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA; Hospital for Special Surgery, New York, NY, USA.
J Biomech. 2023 May;152:111584. doi: 10.1016/j.jbiomech.2023.111584. Epub 2023 Apr 11.
Tendinopathies are common injuries that typically occur from overuse and fatigue. Treatments target late-stage symptoms with limited success, leading to high rates of reinjury. Early intervention could halt tendinopathy progression to rupture but requires a better understanding of the biomechanical environment associated with early-stage disease. While fatigue injured tendons are further damaged by exercise that is initiated immediately after onset of injury, exercise that is initiated after a brief delay promotes repair. Similar macroscale mechanical properties and collagen damage throughout this delay period suggests that microscale, non-collagenous matrix changes after fatigue injury modulate tendon mechanotransduction and shifts the exercise response from detrimental to reparative. Glycosaminoglycans (GAGs) and proteoglycans (PGs) are increased during chronic tendinopathy, but their role in early-stage disease is unknown. We hypothesized that increased GAGs from fatigue injury modulate viscoelasticity and microscale strains to enable repair from exercise. Various GAG types were increased in the weeks after onset of fatigue injury in the extracellular and pericellular matrices of rat patellar tendons. Enzymatic removal of GAGs from these fatigued tendons increased microscale shear strain, suggesting that GAGs modulate the cell microenvironment after fatigue injury. GAG removal decreased dynamic modulus in the toe region and decreased loss tangent in the linear region of the stress-strain curve in fatigued tendons, suggesting the GAG increase modulates tendon multiscale mechanics and viscoelasticity during fiber uncrimping and fibril sliding and strain transfer. GAGs may influence repair in response to exercise and could serve as a therapeutic target for tendinopathy.
腱病是一种常见的损伤，通常由过度使用和疲劳引起。治疗方法针对晚期症状，但效果有限，导致再损伤率较高。早期干预可能阻止腱病进展为破裂，但需要更好地了解与早期疾病相关的生物力学环境。虽然疲劳损伤的肌腱在受伤后立即开始运动时会进一步受损，但在短暂延迟后开始的运动可以促进修复。在这段延迟期间，相似的宏观力学性能和胶原损伤表明，疲劳损伤后微尺度、非胶原基质的变化调节了腱的机械转导，并将运动反应从有害转变为修复。糖胺聚糖 (GAGs) 和蛋白聚糖 (PGs) 在慢性腱病中增加，但它们在早期疾病中的作用尚不清楚。我们假设疲劳损伤后的 GAGs 增加调节粘弹性和微尺度应变，从而使运动能够进行修复。在大鼠髌腱的细胞外基质和细胞周基质中，各种 GAG 类型在疲劳损伤后的几周内增加。从这些疲劳肌腱中去除 GAGs 会增加微尺度剪切应变，这表明 GAGs 调节疲劳损伤后的细胞微环境。GAG 去除会增加疲劳肌腱中脚趾区域的动态模量，并降低线性区域的损耗角正切，这表明 GAG 增加调节肌腱多尺度力学和粘弹性，在纤维解捻和原纤维滑动以及应变传递过程中。GAGs 可能会影响对运动的修复反应，并且可以作为腱病的治疗靶点。
