Department of Biomedical Engineering, National Taiwan University, Taipei 10617, Taiwan.
Departments of Physical Medicine and Rehabilitation, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10048, Taiwan.
Int J Mol Sci. 2019 Jul 12;20(14):3437. doi: 10.3390/ijms20143437.
Because of limitations in the current understanding of the exact pathogenesis of tendinopathy, and the lack of an optimal experimental model, effective therapy for the disease is currently unavailable. This study aims to prove that repression of oxidative stress modulates the differentiation of tendon-derived cells (TDCs) sustaining excessive tensile strains, and proposes a novel bioreactor capable of applying differential tensile strains to cultured cells simultaneously. TDCs, including tendon-derived stem cells, tenoblasts, tenocytes, and fibroblasts, were isolated from the patellar tendons of Sprague‒Dawley rats. Cyclic uniaxial stretching with 4% or 8% strain at 0.5 Hz for 8 h was applied to TDCs. TDCs subjected to 8% strain were treated with epigallocatechin gallate (EGCG), piracetam, or no medication. Genes representing non-tenocyte lineage (, , and ) and type I and type III collagen were analyzed by quantitative polymerase chain reaction. The 8% strain group showed increased expression of non-tenocyte lineage genes and type III/type I collagen ratios compared with the control and 4% strain groups, and the increased expression was ameliorated with addition of EGCG and piracetam. The model developed in this work could be applied to future research on the pathophysiology of tendinopathy and development of treatment options for the disease. Repression of oxidative stress diminishes the expression of genes indicating aberrant differentiation in a rat cell model, which indicates potential therapeutic intervention of tendinopathy, the often relentlessly degenerate condition.
由于目前对肌腱病的确切发病机制的理解有限，而且缺乏理想的实验模型，因此目前还没有有效的治疗方法。本研究旨在证明抑制氧化应激可调节承受过度拉伸应变的肌腱源性细胞（TDC）的分化，并提出一种新型生物反应器，能够同时对培养细胞施加差异拉伸应变。TDC 包括肌腱源性干细胞、腱细胞、肌腱细胞和成纤维细胞，从 Sprague-Dawley 大鼠的髌腱中分离出来。对 TDC 施加 0.5 Hz 频率的 4%或 8%应变的循环单轴拉伸，持续 8 小时。对 8%应变组的 TDC 用表没食子儿茶素没食子酸酯（EGCG）、吡拉西坦或不进行药物治疗。通过定量聚合酶链反应分析代表非肌腱细胞谱系（、和）以及 I 型和 III 型胶原的基因。与对照组和 4%应变组相比，8%应变组表现出非肌腱细胞谱系基因和 III 型/ I 型胶原比值的表达增加，而添加 EGCG 和吡拉西坦可改善这种增加。本工作中开发的模型可应用于肌腱病病理生理学的未来研究和疾病治疗选择的开发。抑制氧化应激可减少大鼠细胞模型中异常分化基因的表达，这表明对肌腱病这种常呈进行性退化的疾病有潜在的治疗干预作用。
