Wnt5a mediated canonical Wnt signaling pathway activation in orthodontic tooth movement: possible role in the tension force-induced bone formation
Wnt5a mediated canonical Wnt signaling pathway activation in orthodontic tooth movement: possible role in the tension force-induced bone formation
复制标题
Wnt5a 介导正畸牙齿移动中典型 Wnt 信号通路激活：在张力诱导的骨形成中可能发挥作用。
DOI：
10.1007/s10735-016-9687-y
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发表时间：
2016-10-01
影响因子：
3.2
通讯作者：
Han, Guang-Li
中科院分区：
文献类型：
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作者：
Fu, Hai-Di;Wang, Bei-Ke;Han, Guang-Li
正畸牙齿移动与正畸机械负荷介导的骨重建有关。越来越多的研究报道，Wnt信号在机械刺激诱导的骨重建中起着重要作用。然而，很少有人知道的参与Wnt信号在正畸力诱导的骨形成过程中OTM。在凭借OTM小鼠模型，如我们以前报道的，其中新骨形成由micro-CT和骨钙素和osterix的免疫反应性确定，我们探讨了Wnt信号通路在OTM过程中的激活。我们的研究结果证实了β-catenin的核转位，提示在张力位点（TS）牙槽骨附近的牙周膜细胞（PDLCs）中，经典的Wnt信号通路被激活。此外，PDLCs中Wnt 5a的免疫反应阳性，而Wnt 3a的免疫反应阴性，表明经典Wnt通路的激活可能是由Wnt 5a介导的，而不是像大多数情况下那样由Wnt 3a介导。通过双标记免疫荧光染色证明的Wnt 5a和β-连环蛋白的共定位进一步支持了该假设。此外，FZD 4和LRP 5在牙周组织TS的PDLCs中高表达，提示Wnt信号通路的激活是由这些受体介导的。ROR 2的可忽略表达也表明Wnt 5a激活了经典而非经典Wnt信号通路，因为先前的研究表明经典/非经典Wnt信号通路的激活在很大程度上依赖于受体。综上所述，我们在此报道了Wnt 5a介导的经典Wnt信号通路的激活可能有助于正畸力诱导的骨重建。
Orthodontic tooth movement (OTM) is associated with bone remodeling mediated by orthodontic mechanical loading. Increasing studies reported that Wnt signaling played crucial roles in mechanical stimuli induced bone remodeling. However, little is known about the involvement of Wnt signaling in orthodontic force-induced bone formation during OTM. In virtue of the OTM mice model as we previously reported, where new bone formation was determined by micro-CT and immunoreactivity of osteocalcin and osterix, we explored the activation of Wnt signaling pathway during OTM. Our results proved the nuclei translocation of beta-catenin, suggesting the activation of canonical Wnt signaling pathway in the periodontal ligament cells (PDLCs) near the alveolar bone at the tension site (TS). Moreover, the immunoreactivity of Wnt5a, but not Wnt3a in PDLCs indicated the activation of canonical Wnt pathway might be mediated by Wnt5a, but not Wnt3a as in most cases. The co-location of Wnt5a and beta-catenin that was evidenced by double labeling immunofluorescence staining further supported the hypothesis. In addition, the high expression of FZD4 and LRP5 in PDLCs at TS of periodontium suggested that the activation of Wnt signaling pathway was mediated by these receptors. The negligible expression of ROR2 also indicated that canonical but not non-canonical Wnt signaling pathway was activated by Wnt5a, since previous studies demonstrated that the activation of canonical/non-canonical Wnt signaling pathway was largely dependent on the receptors. In summary, we here reported that Wnt5a mediated activation of canonical Wnt signaling pathway might contribute to the orthodontic force induced bone remodeling.