The application of mechanical load onto mouse tendons by magnetic restraining represses Mmp-3 expression.

The application of mechanical load onto mouse tendons by magnetic restraining represses Mmp-3 expression.
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DOI:
10.1186/s13104-023-06413-z
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发表时间:
2023-06-30
期刊:
影响因子:
1.8
通讯作者:
--
中科院分区:
其他
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机械负荷是肌腱基质动态平衡的关键。肌腱组织的刺激不足会促进基质的降解,最终导致肌腱失效。在这项研究中,我们检测了肌腱基质分子和基质降解酶(基质金属蛋白酶)在应力剥夺尾部肌腱中的表达,并与通过简单约束方法机械加载的肌腱进行了比较。分离的小鼠尾肌束在细胞培养液中漂浮或被磁铁抑制24小时后,用实时荧光定量RT-PCR方法检测肌腱基质分子和基质金属蛋白酶的基因表达。尾腱应激剥夺可增加Mmp3基因表达水平。约束肌腱抑制了MMP3中的这些增加。由于我们没有观察到我们检测的其他基质相关基因(Col1、Col3、TNC、Acan和Mmp13)的mRNA水平的变化,所以在24小时时,对抑制的基因表达反应是针对Mmp3的。为了阐明肌腱组织中可能调节负荷传递的机制,我们检查了丝状(F-)肌动蛋白染色和核形态。与应力剥夺的肌腱相比,束缚肌腱的F-肌动蛋白染色更深。被束缚的肌腱的核更小,更拉长。这些结果表明,机械负荷可能通过F-肌动蛋白调节细胞核形态来调节特定基因的表达。对Mmp3基因表达调控机制的进一步了解可能会导致预防肌腱退变的新策略。
Mechanical loading is crucial for tendon matrix homeostasis. Under-stimulation of tendon tissue promotes matrix degradation and ultimately tendon failure. In this study, we examined the expression of tendon matrix molecules and matrix-degrading enzymes (matrix metalloproteinases) in stress-deprived tail tendons and compared to tendons that were mechanically loaded by a simple restraining method. Isolated mouse tail fascicles were either floated or restrained by magnets in cell culture media for 24 h. The gene expression of tendon matrix molecules and matrix metalloproteinases in the tendon fascicles of mouse tails were examined by real-time RT-PCR. Stress deprivation of tail tendons increase Mmp3 mRNA levels. Restraining tendons represses these increases in Mmp3. The gene expression response to restraining was specific to Mmp3 at 24 h as we did not observe mRNA level changes in other matrix related genes that we examined (Col1, Col3, Tnc, Acan, and Mmp13). To elucidate, the mechanisms that may regulate load transmission in tendon tissue, we examined filamentous (F-)actin staining and nuclear morphology. As compared to stress deprived tendons, restrained tendons had greater staining for F-actin. The nuclei of restrained tendons are smaller and more elongated. These results indicate that mechanical loading regulates specific gene expression potentially through F-actin regulation of nuclear morphology. A further understanding on the mechanisms involved in regulating Mmp3 gene expression may lead to new strategies to prevent tendon degeneration.
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