Cyclic Stretch Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via YAP Activation
Cyclic Stretch Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via YAP Activation
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循环拉伸通过 YAP 激活增强人牙周膜细胞的成骨分化
DOI：
10.1155/2018/2174824
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Han, Guang-Li
中科院分区：
文献类型：
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作者：
Yang, Yang;Wang, Bei-Ke;Han, Guang-Li
牙周改建和牙槽骨吸收与形成在正畸牙齿移动过程中起着重要作用。在这个过程中，人类牙周韧带细胞(HPDLCs)感知并响应正畸力，促进牙槽骨的形成。然而，这一过程的潜在机制还没有完全阐明。在本研究中，对HPDLCs施加循环应力刺激以模拟OTM过程中的正畸力。我们的结果表明，周期性拉伸促进了人牙周膜细胞的成骨分化。此外，我们的数据表明，同样参与机械信号转导的河马通路效应器YAP被激活，因为我们发现在周期性应激处理的HPDLCs中，YAP的核转位显著增加。YAP靶基因CTGF和CYR61mRNA的表达也显著增加。此外，YAP基因的敲除抑制了周期性拉伸诱导的HPDLCs的成骨，而过表达YAP促进了HPDLCs的成骨。我们还注意到，ROCK和非肌肉肌球蛋白II抑制剂Y-27632和Blebbistatin都可以抑制YAP的活性。这些抑制剂还能显著抑制周期性牵张诱导的HPDLCs成骨。最后，在小鼠OTM模型中，我们的结果显示YAP在张力侧的PDLCs中上调并有核移位。综上所述，我们目前的研究表明，细胞骨架重塑诱导的YAP信号通路的激活在周期性牵张诱导的HPDLCs成骨过程中起关键作用，这可能在OTM过程中发挥重要作用。
Periodontal remodeling and alveolar bone resorption and formation play essential roles during orthodontic tooth movement (OTM). In the process, human periodontal ligament cells (HPDLCs) sense and respond to orthodontic forces, contributing to the alveolar bone formation. However, the underlying mechanism in this process is not fully elucidated. In the present study, cyclic stress stimulus was applied on HPDLCs to mimic the orthodontic forces during OTM. Our results demonstrated that cyclic stretch promoted the osteogenic differentiation of HPDLCs. Moreover, our data suggested that yes-associated protein (YAP), the Hippo pathway effector, which also involved in mechanical signaling transduction, was activated as we found that the nuclear translocation of YAP was significantly increased in the cyclic stress treated HPDLCs. The mRNA expression of CTGF and CYR61, the target genes of YAP, was also remarkably increased. Furthermore, knockdown of YAP suppressed the cyclic stretch induced osteogenesis in HPDLCs, while overexpression of YAP in HPDLCs enhanced osteogenesis. We also noticed that YAP activities could be suppressed by the ROCK and nonmuscle myosin II inhibitors, Y-27632 and Blebbistatin. The inhibitors also significantly inhibited the cyclic stretch induced osteogenesis in HPDLCs. Finally, in the murine OTM model, our results revealed that YAP was upregulated and nuclearly translocated in the PDLCs at the tension side. In summary, our present study demonstrated that cytoskeleton remodeling induced activation of YAP signaling pathway was crucial for the cyclic stretch-induced osteogenesis of HPDLCs, which might play important roles during OTM.