Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk 570749, South Korea.
Cell Biol Int. 2011 Feb;35(2):179-85. doi: 10.1042/CBI20100204.
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 β1 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.
miRNAs（microRNAs）已被证明在多种生物学过程中发挥着重要作用，包括早期发育、细胞增殖和细胞死亡以及细胞分化。然而，关于它们在软骨发生中的潜在作用的信息有限。在本研究中，我们研究了 miRNA-488 在细胞凝聚中的作用，细胞凝聚是软骨分化的必要起始步骤。我们发现，miRNA-488 的表达在预凝聚阶段上调，然后在凝聚后阶段下调。使用基于 PNA（花生凝集素）的 ASO（反义寡核苷酸）阻断 miRNA-488 会降低整合素β1 和磷酸化 FAK（粘着斑激酶）的蛋白水平，从而抑制细胞迁移和运动。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 活性的水平，并且 MMP 抑制剂 GM6001 的共同处理诱导了由 miRNA-488 阻断抑制的细胞凝聚的恢复。总之，我们的结果表明，miRNA-488 是调节细胞与细胞外基质（ECM）相互作用的调节剂之一，通过 MMP-2 调节粘着斑活性，从而在肢体间充质细胞的软骨发生过程中发挥作用。
