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机械负荷的改变会导致 MMP 和 TIMP 表达的肌腱特异性改变:应枯竭和间歇静压对大鼠冈上肌腱和跟腱的影响。

Changes in mechanical loading lead to tendonspecific alterations in MMP and TIMP expression: influence of stress deprivation and intermittent cyclic hydrostatic compression on rat supraspinatus and Achilles tendons.

机构信息

Department of Surgery, University of Calgary, 451A Heritage Medical Research Building, 3330 Hospital Dr NW, Calgary, Alberta T2N4N1, Canada.

出版信息

Br J Sports Med. 2010 Aug;44(10):698-703. doi: 10.1136/bjsm.2008.050575. Epub 2008 Sep 18.

Abstract

BACKGROUND

Tendinopathy commonly occurs in tendons with large in vivo loading demands like the Achilles tendon (AT) and supraspinatus tendon (SST). In addition to differences in their local anatomic environment, these tendons are designed for different loading requirements because of the muscles to which they attach, with the AT experiencing higher loads than the SST. One possible factor in the progression of tendinopathy is the interplay between mechanical loading and the regulation of enzymes that degrade the extracellular matrix (matrix metalloproteinases (MMPs)) and their inhibitors (tissue inhibitor of metalloprotienases (TIMPs)). Thus, overuse injuries may have different biological consequences in tendons designed for different in vivo loading demands.

AIM

In this study, the tendon-specific regulation of MMP-13, MMP-3 and TIMP-2 expression in rat AT and SST exposed to two different mechanical environments was investigated.

METHODS

Rat AT and SST were exposed to stress deprivation (ie, detached from attachments) and intermittent cyclic hydrostatic compression (with attachments intact). Levels of MMP-13, MMP-3 and TIMP-2 mRNA were evaluated in time-zero control, attached, stressdeprived and "compressed" tendons.

RESULTS

Stress deprivation led to elevated expression of MMP-13, MMP-3 and TIMP-2 in both tendons, although the magnitude of the increase was greater for the SST than the AT. Intermittent cyclic hydrostatic compression of attached tendons increased expression of MMP-13 in the SST, but not the AT.

CONCLUSIONS

The results of this study suggest that stress deprivation may be one contributor to the progression of tendinopathy in AT and SST, where the tendon designed for the lower in vivo loading demand (SST) was the most affected by a change in mechanical loading. The unique upregulation of MMP-13 with hydrostatic compression supports the impingement injury theory for rotator cuff tears.

摘要

背景

腱病常发生于体内负荷较大的肌腱,如跟腱(AT)和冈上肌腱(SST)。除了局部解剖环境的差异外,这些肌腱的设计也适应于不同的负荷要求,因为它们附着的肌肉不同,AT 所承受的负荷高于 SST。腱病进展的一个可能因素是机械负荷与调节细胞外基质(基质金属蛋白酶(MMPs))及其抑制剂(金属蛋白酶组织抑制剂(TIMPs))降解酶之间的相互作用。因此,过度使用损伤在适应不同体内负荷要求的肌腱中可能具有不同的生物学后果。

目的

本研究旨在探讨在两种不同力学环境下,大鼠 AT 和 SST 中 MMP-13、MMP-3 和 TIMP-2 的表达的肌腱特异性调节。

方法

将大鼠 AT 和 SST 暴露于应力剥夺(即与附着点分离)和间歇性循环液压压缩(附着点完整)两种不同的力学环境中。在时间零对照、附着、应力剥夺和“压缩”肌腱中评估 MMP-13、MMP-3 和 TIMP-2 mRNA 的水平。

结果

应力剥夺导致两种肌腱中 MMP-13、MMP-3 和 TIMP-2 的表达升高,尽管 SST 的升高幅度大于 AT。附着肌腱的间歇性循环液压压缩增加了 SST 中 MMP-13 的表达,但 AT 中没有增加。

结论

本研究结果表明,应力剥夺可能是 AT 和 SST 腱病进展的一个原因,其中设计用于较低体内负荷需求的肌腱(SST)受机械负荷变化的影响最大。液压压缩导致 MMP-13 的独特上调支持肩袖撕裂的撞击损伤理论。

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