Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, China.
Orthodontic Centre, West China College of Stomatology, Sichuan University, Chengdu, China.
J Cell Physiol. 2019 Apr;234(4):5086-5096. doi: 10.1002/jcp.27312. Epub 2018 Oct 20.
During orthodontic tooth movement (OTM), periodontal ligament cells (PDLCs) receive the mechanical stimuli and transform it into myofibroblasts (Mfbs). Indeed, previous studies have demonstrated that mechanical stimuli can promote the expression of Mfb marker α-smooth muscle actin (α-SMA) in PDLCs. Transforming growth factor β1 (TGF-β1), as the target gene of yes-associated protein (YAP), has been proven to be involved in this process. Here, we sought to assess the role of YAP in Mfbs differentiation from PDLCs. The time-course expression of YAP and α-SMA was manifested in OTM model in vivo as well as under tensional stimuli in vitro. Inhibition of RhoA/Rho-associated kinase (ROCK) pathway using Y27632 significantly reduced tension-induced Mfb differentiation and YAP expression. Moreover, overexpression of YAP with lentiviral transfection in PDLCs rescued the repression effect of Mfb differentiation induced by Y27632. These data together suggest a crucial role of YAP in regulating tension-induced Mfb differentiation from PDLC interacted with RhoA/ROCK pathway.
在正畸牙齿移动(OTM)过程中,牙周膜细胞(PDLCs)接收机械刺激并将其转化为肌成纤维细胞(Mfbs)。事实上,先前的研究已经表明,机械刺激可以促进 PDLCs 中肌成纤维细胞标志物α-平滑肌肌动蛋白(α-SMA)的表达。转化生长因子β1(TGF-β1)作为 yes 相关蛋白(YAP)的靶基因,已被证明参与了这一过程。在这里,我们试图评估 YAP 在 PDLCs 向肌成纤维细胞分化中的作用。YAP 和 α-SMA 的时程表达在体内 OTM 模型以及体外张力刺激下均有表现。使用 Y27632 抑制 RhoA/ Rho 相关激酶(ROCK)通路显著减少了张力诱导的肌成纤维细胞分化和 YAP 表达。此外,用慢病毒转染过表达 YAP 可挽救 Y27632 诱导的肌成纤维细胞分化抑制作用。这些数据共同表明,YAP 在调节 RhoA/ROCK 通路相互作用的张力诱导的 PDLC 向肌成纤维细胞分化中起关键作用。