Ex vivo static tensile loading inhibits MMP-1 expression in rat tall tendon cells through a cytoskeletally based mechanotransduction mechanism

Ex vivo static tensile loading inhibits MMP-1 expression in rat tall tendon cells through a cytoskeletally based mechanotransduction mechanism
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DOI:
10.1016/s0736-0266(03)00185-2
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发表时间:
2004-03-01
影响因子:
2.8
通讯作者:
Gardner, K
Gardner, K
中科院分区:
医学3区
文献类型:
--
作者:
Arnoczky, SP;Tian, T;Gardner, K

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为研究不同程度的体外静态拉伸负荷对肌腱细胞胶原酶(MMP-1)表达的影响,将大鼠尾肌腱在0.16、0.77、1.38和2.6MPa的张力下静态加载24 h。采用北方印迹分析法检测新鲜、24 h负荷剥夺和24 h静态负荷肌腱中MMP-1 mRNA的表达。采用Western blot法检测新鲜肌腱和24 h负荷剥夺肌腱中MMP-1原和MMP-1蛋白的表达。新鲜收获的大鼠尾肌腱表现出没有证据的MMP-1 mRNA的表达和没有证据的pro-MMP-1或MMP-1蛋白。离体负荷剥夺24 h导致MMP-1的mRNA表达显著增加,这与MMP-1前体和MMP-1蛋白表达的显著增加相一致。当肌腱在24 h培养期间经受离体静态拉伸负荷时,发现随着负荷的增加,MMP-1 mRNA表达的上调被显著抑制(p < 0.05)。MMP-1的表达与静态拉伸负荷水平呈显著负相关(r(2)= 0.78)和显著负相关(p < 0.001)。用细胞松弛素D破坏肌动蛋白细胞骨架可消除离体静态拉伸负荷对MMP-1表达的抑制作用。这项研究的结果表明,MMP-1的表达上调肌腱细胞离体可以抑制静态拉伸负荷,大概是通过一个cytoplanally为基础的mechanotransduction途径。(C)2003骨科研究学会。由爱思唯尔有限公司出版。保留所有权利。
To determine the effect of various degrees of ex vivo static tensile loading on the expression of collagenase (MMP-1) in tendon cells, rat tail tendons were statically loaded in tension at 0.16, 0.77, 1.38 or 2.6 MPa for 24 h. Northern blot analysis was used to assay for mRNA expression of MMP-1 in freshly harvested, 24 h load deprived, and 24 h statically loaded tendons. Western blot analysis was used to assay for pro-MMP-1 and MMP-1 protein expression in fresh and 24 h load deprived tendons. Freshly harvested rat tail tendons demonstrated no evidence of MMP-1 mRNA expression and no evidence of the pro-MMP-1 or MMP-1 protein. Ex vivo load deprivation for 24 h resulted in a marked increase in the mRNA expression of MMP-1 which coincided with a marked increase of both pro-MMP-1 and MMP-1 protein expression. When tendons were subjected to ex vivo static tensile loading during the 24 h culture period, a significant inhibition of this upregulation of MMP-1 mRNA expression was found with increasing load (p < 0.05). A strong (r(2) = 0.78) and significant (p < 0.001) inverse correlation existed between the level of static tensile load and the expression of MMP-1. Disruption of the actin cytoskeleton with cytochalasin D abolished the inhibitory effect of ex vivo static tensile loading on MMP-1 expression. The results of this study suggest that up-regulation of MMP-1 expression in tendon cells ex vivo can be inhibited by static tensile loading, presumably through a cytoskeletally based mechanotransduction pathway. (C) 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.