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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：由逐渐生理机制对工程肌肉产生的机械压缩引起的细胞死亡

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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：由于持续的机械载荷，深层组​​织损伤（DTI），一种压力溃疡，在骨骼突出等肌层中产生。 DTI在诊所呈现出严重的问题，因为它通常不可见，直到达到高级阶段。其中一种原因可以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缩诱导的细胞死亡机制。通过将重量放在构造的顶部来施加压缩。研究了细胞骨架的形态变化和丝裂剂活化蛋白激酶（MAPK）的磷酸化。此外，对于三个主要MAPK组，P38，ERK和JNK中的每一个的抑制剂分别应用，以查看压缩中的作用导致细胞凋亡和坏死。本研究首次表明直接机械压缩激活MAPK磷酸化。压缩还导致细胞骨架的逐渐破坏。通过P38和JNK抑制剂缩小到卸载组的水平，细胞凋亡率强烈降低。在启动压缩后，可以在24小时内观察到这种现象。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由生理机制引起，而不是通过直接杀死细胞的物理机制。这些发现揭示了机械压缩下肌细胞死亡的洞察力。此外，结果表明，通过用P38或/和JNK抑制剂预处理预防DTI的潜在临床解决方案。 （c）2016 Elsevier Ltd.保留所有权利。

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