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首页> 外文期刊>Journal of Biomechanics >Cell death induced by mechanical compression on engineered muscle results from a gradual physiological mechanism
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Cell death induced by mechanical compression on engineered muscle results from a gradual physiological mechanism

机译：机械加压对工程肌肉造成的细胞死亡是由逐渐的生理机制引起的

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Deep tissue injury (DTI), a type of pressure ulcer, arises in the muscle layers adjacent to bony prominences due to sustained mechanical loading. DTI presents a serious problem in the clinic, as it is often not visible until reaching an advanced stage. One of the causes can be direct mechanical deformation of the muscle tissue and cell. The mechanism of cell death induced by mechanical compression was studied using bio-artificial skeletal muscle tissues. Compression was applied by placing weights on top of the constructs. The morphological changes of the cytoskeleton and the phosphorylation of mitogen-activated protein kinases (MAPK) under compression were investigated. Moreover, inhibitors for each of the three major MAPK groups, p38, ERK, and JNK, were applied separately to look at their roles in the compression caused apoptosis and necrosis. The present study for the first time showed that direct mechanical compression activates MAPK phosphorylation. Compression also leads to a gradual destruction of the cytoskeleton. The percentage apoptosis is strongly reduced by p38 and JNK inhibitors down to the level of the unloaded group. This phenomenon could be observed up to 24 h after initiation of compression. Therefore, cell death in bio-artificial muscle tissue caused by mechanical compression is primarily caused by a physiological mechanism, rather than through a physical mechanism which kills the cell directly. These findings reveal insight of muscle cell death under mechanical compression. Moreover, the result indicates a potential clinical solution to prevent DTI by pre-treating with p38 or/and JNK inhibitors. (C) 2016 Elsevier Ltd. All rights reserved.
机译：由于持续的机械负荷，深部组织损伤（DTI）是一种压力性溃疡，出现在邻近骨突出的肌肉层中。 DTI在临床上提出了一个严重的问题，因为它通常要到高级阶段才能看到。原因之一可能是肌肉组织和细胞的直接机械变形。使用生物人工骨骼肌组织研究了机械压迫诱导的细胞死亡机制。通过将重物置于构建体的顶部来施加压缩。研究了压缩状态下细胞骨架的形态变化和丝裂原活化蛋白激酶（MAPK）的磷酸化。此外，分别应用了三个主要MAPK组（p38，ERK和JNK）的抑制剂，以查看它们在受压引起的细胞凋亡和坏死中的作用。本研究首次表明直接机械压缩可激活MAPK磷酸化。压缩还导致细胞骨架的逐渐破坏。 p38和JNK抑制剂可将细胞凋亡百分比显着降低至无负荷组水平。这种现象可以在开始压缩后长达24小时内观察到。因此，由机械压缩引起的生物-人工肌肉组织中的细胞死亡主要是由生理机制引起的，而不是由直接杀死细胞的物理机制引起的。这些发现揭示了机械压缩下肌肉细胞死亡的见解。此外，该结果表明通过用p38或/和JNK抑制剂进行预处理来预防DTI的潜在临床解决方案。 （C）2016 Elsevier Ltd.保留所有权利。

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