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MicroRNA-488 suppresses cell migration through modulation of the focal adhesion activity during chondrogenic differentiation of chick limb mesenchymal cells

机译:MicroRNA-488通过调节鸡肢间充质细胞软骨分化过程中的粘着活性抑制细胞迁移

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miRNAs (microRNAs) have proven to play essential roles in diverse biological processes including early development, cell proliferation and cell death, and cell differentiation. However, there is only limited amount of information about their potential role in chondrogenesis. In the present study, we investigated the role of miRNA-488 in the cellular condensation, which is essential initiation for chondrogenic differentiation. We found that miRNA-488 expression is up-regulated at the precondensation stage and then down-regulated at the postcondensation stage. Blockade of miRNA-488 via the use of PNA (peanut agglutinin)-based ASOs (antisense oligonucleotides) decreased the protein level of integrins beta1 and phosphorylated FAK (focal adhesion kinase) and resulted in the suppression of cell motility and migration. Moreover, in parallel with theses observation, treatment of anti-miRNA-488 oligonucleotides up-regulated the level of MMP (matrix metalloprotease)-2 activity, and co-treatment with GM6001, an MMP inhibitor, induced recovery of cellular condensation inhibited by blockade of miRNA-488. Collectively, our results suggest that miRNA-488 is one of regulator in cell to ECM (extracellular matrix) interaction through modulation of focal adhesion activity by MMP-2 during chondrogenesis of limb mesenchymal cells.
机译:事实证明,miRNA(microRNA)在包括早期发育,细胞增殖和细胞死亡以及细胞分化在内的多种生物学过程中起着至关重要的作用。但是,关于它们在软骨形成中潜在作用的信息很少。在本研究中,我们研究了miRNA-488在细胞凝结中的作用,这是软骨分化的重要起点。我们发现,miRNA-488表达在缩合前阶段上调,然后在缩合后阶段下调。通过使用基于PNA(花生凝集素)的ASO(反义寡核苷酸)对miRNA-488进行的封锁降低了整联蛋白beta1和磷酸化FAK(黏着斑激酶)的蛋白质水平,并导致细胞运动和迁移受到抑制。此外,与这些观察结果平行的是,抗miRNA-488寡核苷酸的处理上调了MMP(基质金属蛋白酶)-2的活性,并与MMP抑制剂GM6001共同处理,诱导了受阻滞抑制的细胞凝缩的恢复。 miRNA-488。总体而言,我们的研究结果表明,miRNA-488是肢体间充质细胞软骨形成过程中通过MMP-2调节粘着斑活性来调节细胞与ECM(细胞外基质)相互作用的调节剂之一。

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