Department of Mechanical Science and Engineering, Nagoya University, Nagoya, Japan.
J Cell Physiol. 2012 Jun;227(6):2722-9. doi: 10.1002/jcp.23016.
Human bone marrow mesenchymal stem cells (hMSCs) have the potential to differentiate into tendon/ligament-like lineages when they are subjected to mechanical stretching. However, the means through which mechanical stretch regulates the tenogenic differentiation of hMSCs remains unclear. This study examined the role of RhoA/ROCK, cytoskeletal organization, and focal adhesion kinase (FAK) in mechanical stretch-induced tenogenic differentiation characterized by the up-regulation of tendon-related marker gene expression. Our findings showed that RhoA/ROCK and FAK regulated mechanical stretch-induced realignment of hMSCs by regulating cytoskeletal organization and that RhoA/ROCK and cytoskeletal organization were essential to mechanical stretch-activated FAK phosphorylation at Tyr397. We also demonstrated that this process can be blocked by Y-27632 (a specific inhibitor of RhoA/ROCK), cytochalasin D (an inhibitor of cytoskeletal organization) or PF 573228 (a specific inhibitor of FAK). The results of this study suggest that RhoA/ROCK, cytoskeletal organization, and FAK compose a "signaling network" that senses mechanical stretching and drives mechanical stretch-induced tenogenic differentiation of hMSCs. This work provides novel insights regarding the mechanisms of tenogenesis in a stretch-induced environment and supports the therapeutic potential of hMSCs.
人骨髓间充质干细胞（hMSCs）在受到机械拉伸时，有可能分化为肌腱/韧带样谱系。然而，机械拉伸调节 hMSCs 向肌腱分化的方式仍不清楚。本研究探讨了 RhoA/ROCK、细胞骨架组织和粘着斑激酶（FAK）在机械拉伸诱导的肌腱相关标记基因表达上调的肌腱分化中的作用。我们的研究结果表明，RhoA/ROCK 和 FAK 通过调节细胞骨架组织来调节机械拉伸诱导的 hMSC 重新排列，并且 RhoA/ROCK 和细胞骨架组织对于机械拉伸激活 FAK 在 Tyr397 的磷酸化是必需的。我们还证明，这个过程可以被 Y-27632（RhoA/ROCK 的特异性抑制剂）、细胞松弛素 D（细胞骨架组织的抑制剂）或 PF 573228（FAK 的特异性抑制剂）阻断。本研究的结果表明，RhoA/ROCK、细胞骨架组织和 FAK 组成了一个“信号网络”，可以感知机械拉伸并驱动 hMSCs 的机械拉伸诱导的肌腱分化。这项工作为拉伸诱导环境中的肌腱发生机制提供了新的见解，并支持了 hMSCs 的治疗潜力。
