Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
Chongqing Engineering Research Center of Medical Electronics and Information Technology, College of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing 400065, China.
Int J Mol Sci. 2021 May 6;22(9):4928. doi: 10.3390/ijms22094928.
The mechanosensitive gene tenomodulin (Tnmd) is implicated in tendon maturation and repair. However, the mechanism by which mechanical loading regulates Tnmd's expression and its role in tenocyte migration is yet to be defined. Here, we show that Tnmd and migration were upregulated in uniaxial cyclic stress-stimulated tenocytes. The knockdown of Tnmd reduced cell migration in the presence and absence of mechanical loading, suggesting that Tnmd is involved in tenocyte migration. Moreover, the treatment of stress-stimulated tenocytes with the actin inhibitor latrunculin (Lat A), histone acetyltransferase inhibitor anacardic acid (ANA), or histone demethylases inhibitor GSK-J4 suppressed Tnmd expression and tenocyte migration. These results show that actin stress fiber formation and chromatin decondensation regulates Tnmd expression, which might then regulate tenocyte migration. Thus, this study proposes the involvement of the actin and chromatin mechanotransduction pathway in the regulation of Tnmd and reveals a novel role of Tnmd in tenocyte migration. The identification of Tnmd function in tenocyte migration provides insight into the molecular mechanisms involved in Tnmd-mediated tendon repair.
机械敏感基因腱调蛋白（Tnmd）参与肌腱成熟和修复。然而，机械负荷调节 Tnmd 表达的机制及其在肌腱细胞迁移中的作用尚待确定。在这里，我们表明，在单轴循环应力刺激的肌腱细胞中，Tnmd 和迁移被上调。Tnmd 的敲低减少了机械加载存在和不存在时的细胞迁移，这表明 Tnmd 参与了肌腱细胞的迁移。此外，用肌动蛋白抑制剂拉曲库林（Lat A）、组蛋白乙酰转移酶抑制剂漆酚（ANA）或组蛋白去甲基化酶抑制剂 GSK-J4 处理应激刺激的肌腱细胞，抑制了 Tnmd 的表达和肌腱细胞的迁移。这些结果表明，肌动蛋白应力纤维形成和染色质去凝聚调节 Tnmd 的表达，从而可能调节肌腱细胞的迁移。因此，本研究提出了肌动蛋白和染色质机械转导途径在 Tnmd 调节中的参与，并揭示了 Tnmd 在肌腱细胞迁移中的新作用。Tnmd 在肌腱细胞迁移中的功能鉴定为 Tnmd 介导的肌腱修复涉及的分子机制提供了深入了解。
