The expression and regulation of Wnt1 in tooth movement-initiated mechanotransduction
The expression and regulation of Wnt1 in tooth movement-initiated mechanotransduction
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DOI：
10.1016/j.ajodo.2020.08.006
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发表时间：
2020-12-01
影响因子：
3
通讯作者：
Kamiokaa, Hiroshi
中科院分区：
文献类型：
--
作者：
Hlaing, Ei Ei Hsu;Ishihara, Yoshihito;Kamiokaa, Hiroshi
简介：Wnt信号通路是骨骼发育及其稳态的关键调节因子。然而，Wnt 1在正畸牙齿移动引发的骨重建的机械转导机制中的潜在作用仍不清楚。因此，本研究的重点是在牙周膜（PDL）和骨细胞在体内和体外的Wnt 1表达的调控动力学。研究方法：在0，1，和5天，在压缩和张力侧的小鼠上颌第一磨牙中的Wnt 1表达进行了评估。将原代分离的人PDL（hPDL）成纤维细胞以及鼠长骨骨细胞-Y 4（MLO-Y 4）细胞暴露于连续压缩力和静态拉伸力。结果如下：免疫检测的相对定量显示，正畸牙齿移动显着刺激Wnt 1的表达在两个PDL和牙槽骨细胞的张力侧在第5天，而在压缩侧的表达没有改变。在分离的hPDL成纤维细胞中施加12%的静态张力和在MLO-Y 4细胞中施加20%的静态张力后，也注意到体内显示的Wnt 1表达的这种增加。相反，压缩力导致Wnt 1基因在hPDL成纤维细胞和MLO-Y 4细胞中的表达以力依赖性方式减弱。在骨细胞-PDL共培养系统中，重组sclerostin减弱PDL中的Wnt 1，而抗sclerostin抗体上调其基因表达，表明PDL中机械驱动的Wnt 1信号可能受骨细胞sclerostin调节。结论：我们的研究结果表明，Wnt 1信号通过创新的机械转导方法在牙齿移动引发的骨重建中起着至关重要的作用。
Introduction: The Wnt signaling pathway acts as a key regulator of skeletal development and its homeostasis. However, the potential role of Wnt1 in the mechanotransduction machinery of orthodontic tooth movement-initiated bone remodeling is still unclear. Hence, this study focused on the regulatory dynamics of the Wnt1 expression in both the periodontal ligament (PDL) and osteocytes in vivo and in vitro. Methods: The Wnt1 expression in the orthodontically moved maxillary first molar in mice was assessed at 0, 1, and 5 days, on both the compression and tension sides. Primary isolated human PDL (hPDL) fibroblasts, as well as murine long-bone osteocyte-Y4 (MLO-Y4) cells, were exposed to continuous compressive force and static tensile force. Results: The relative quantification of immunodetection showed that orthodontic tooth movement significantly stimulated the Wnt1 expression in both the PDL and alveolar osteocytes on the tension side on day 5, whereas the expression on the compression side did not change. This increase in the Wnt1 expression, shown in vivo, was also noted after the application of 12% static tensile force in isolated hPDL fibroblasts and 20% in MLO-Y4 cells. In contrast, a compressive force led to the attenuation of the Wnt1 gene expression in both hPDL fibroblasts and MLO-Y4 cells in a force-dependent manner. In the osteocyte-PDL coculture system, recombinant sclerostin attenuated Wnt1 in PDL, whereas the antisclerostin antibody upregulated its gene expression, indicating that mechanically-driven Wnt1 signaling in PDL might be regulated by osteocytic sclerostin. Conclusions: Our findings provide that Wnt1 signaling plays a vital role in tooth movement-initiated bone remodeling via innovative mechanotransduction approaches.