Cyclic loading inhibits expression of MMP-3 but not MMP-1 in an in vitro rabbit flexor tendon model

Cyclic loading inhibits expression of MMP-3 but not MMP-1 in an in vitro rabbit flexor tendon model
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DOI:
10.1016/j.clinbiomech.2007.08.007
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发表时间:
2008-01-01
影响因子:
1.8
通讯作者:
Rempel, David M.
Rempel, David M.
中科院分区:
工程技术3区
文献类型:
--
作者:
Asundi, Krishna R.;Rempel, David M.

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背景基因表达分析有助于评估细胞行为,并可能提高我们对导致肌腱退变的机械负荷的初始细胞反应的理解。本研究评估了MMP-1和MMP-3的基因表达,与基质降解相关的基因,在肌腱暴露于生理范围内的周期性负荷。从10只新西兰白色兔中的每只中收获6个屈肌腱,并随机分配到以下6组之一:负荷剥夺18 h;循环负荷18 h至峰值应力2 MPa; 3 MPa; 4 MPa; 5 MPa;或在液氮中速冻。用qRT-PCR检测MMP-1、MMP-3和18 s mRNA的表达。MMP-1 mRNA表达水平在负荷组之间无显著差异。MMP-3的表达显着抑制(57%)在肌腱循环加载到4 MPa的峰值应力相比,负载剥夺肌腱,然而,当峰值应力增加到5 MPa,表达不再显着低于应力屏蔽肌腱。结果表明,负荷与MMP-3表达之间呈“U”形关系。MMP-1表达随负荷的缺乏变化是出乎意料的,因为在先前的研究中已经证明了MMP-1响应于机械负荷的抑制。总之,我们表明,MMP-3的表达是调制的循环负荷,是敏感的负荷大小。MMP-1 mRNA的表达在该模型中不受循环负荷的显著调节。(C)2007爱思唯尔有限公司保留所有权利。
Background. Gene expression analysis is useful for assessing cellular behavior and may improve our understanding of the initial cellular response to mechanical load leading to tendon degeneration. This study assessed gene expression of MMP-1 and MMP-3, genes associated with matrix degradation, in tendons exposed to cyclic loads within physiologic range.Methods. Six flexor tendons from each of ten New Zealand White rabbits were harvested and randomly assigned to one of the following six groups: load deprived for 18 h; cyclically loaded for 18 h to a peak stress of 2 MPa; 3 MPa; 4 MPa; 5 MPa; or snap frozen in liquid nitrogen. MMP-1, MMP-3 and 18 s mRNA expression was measured by qRT-PCR.Findings. No significant differences in MMP-1 mRNA expression levels were found between loading groups. MMP-3 expression was significantly inhibited (57%) in tendons cyclically loaded to a peak stress of 4 MPa in comparison to load deprived tendons, however, when peak stress was increased to 5 MPa, expression was no longer significantly lower compared to stress shielded tendons.Interpretation. The results suggest a 'U' shape relationship between load and MMP-3 expression. The lack of change in MMP-1 expression with loading was unexpected as inhibition of MMP-1 in response to mechanical load has been demonstrated in previous studies. In conclusion, we demonstrate that MMP-3 expression is modulated by cyclic load and is sensitive to load magnitude. MMP-1 mRNA expression is not significantly modulated by cyclic load in this model. (C) 2007 Elsevier Ltd. All rights reserved.