Controlled treadmill exercise eliminates chondroid deposits and restores tensile properties in a new murine tendinopathy model
Controlled treadmill exercise eliminates chondroid deposits and restores tensile properties in a new murine tendinopathy model
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DOI：
10.1016/j.jbiomech.2012.10.020
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发表时间：
2013-02-01
影响因子：
2.4
通讯作者：
Wang, Vincent M.
中科院分区：
文献类型：
--
作者：
Bell, Rebecca;Li, Jun;Wang, Vincent M.
肌腱病是一种广泛的致残性疾病，其特征是胶原纤维破坏和富含糖胺聚糖的软骨样基质积聚。最近的临床报告已经说明了机械负荷（运动）疗法成功治疗慢性肌腱病的潜力。我们已经开发了一种新的小鼠肌腱病模型，该模型需要将TGF-β 1单次注射到跟腱中间物质中，然后进行正常的笼活动2周。在这个时候，肌腱最大应力显示出显着的（66%）减少相对于正常对照组，并持续在四周。材料特性的丧失伴随着肌腱内丰富的软骨样细胞（与术中获得的人体样本中观察到的变化非常相似）以及Acan、Col 1a 1、Col 2a 1、Col 3a 1、Fn 1和Mmp 3表达的增加。在注射TGF-β 1后每天进行两周跑步机运动的小鼠显示出与笼中组相似的肌腱材料性质的降低。然而，在小鼠进行4周的跑步机运动，肌腱最大应力值是类似的幼稚控制。运动4周的小鼠肌腱基本上没有软骨样细胞，Acan、Col 1a 1、Col 2a 1、Col 3a 1和Mmp 3的表达相对于4周笼组显著降低。这种技术上简单的鼠肌腱病模型非常适合于生物力学和细胞生物学途径的详细机制和转化研究，可以靶向增强肌腱病的愈合。(C)2012爱思唯尔有限公司保留所有权利。
Tendinopathy is a widespread and disabling condition characterized by collagen fiber disruption and accumulation of a glycosaminoglycan-rich chondroid matrix. Recent clinical reports have illustrated the potential of mechanical loading (exercise) therapies to successfully treat chronic tendinopathies. We have developed a new murine tendinopathy model which requires a single injection of TGF-beta 1 into the Achilles tendon midsubstance followed by normal cage activity for 2 weeks. At this time, tendon maximum stress showed a dramatic (66%) reduction relative to that of normal controls and this persisted at four weeks. Loss of material properties was accompanied by abundant chondroid cells within the tendon (closely resembling the changes observed in human samples obtained intra-operatively) and increased expression of Acan, Col1a1, Col2a1, Col3a1, Fn1 and Mmp3. Mice subjected to two weeks of daily treadmill exercise following TGF-beta 1 injection showed a similar reduction in tendon material properties as the caged group. However, in mice subjected to 4 weeks of treadmill exercise, tendon maximum stress values were similar to those of naive controls. Tendons from the mice exercised for 4 weeks showed essentially no chondroid cells and the expression of Acan, Col1a1, Col2a1, Col3a1, and Mmp3 was significantly reduced relative to the 4-week cage group. This technically simple murine tendinopathy model is highly amenable to detailed mechanistic and translational studies of the biomechanical and cell biological pathways, that could be targeted to enhance healing of tendinopathy. (C) 2012 Elsevier Ltd. All rights reserved.