Role of Osteocyte-PDL Crosstalk in Tooth Movement via SOST/Sclerostin
Role of Osteocyte-PDL Crosstalk in Tooth Movement via SOST/Sclerostin
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DOI：
10.1177/0022034518771331
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发表时间：
2018-11-01
影响因子：
7.6
通讯作者：
Kamioka, H.
中科院分区：
文献类型：
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作者：
Odagaki, N.;Ishihara, Y.;Kamioka, H.
硬化蛋白（Scl）负性调节骨形成并促进骨吸收。骨细胞是负责机械感受的细胞，已知是Scl的主要来源，并且是通过诱导NF-κ B配体受体激活剂（RANKL）进行骨重建的关键调节剂。然而，Scl在响应机械刺激的时空模式及其调节机制仍然未知。我们研究了正畸牙齿移动（OTM）在体内和体外产生的SOST/Scl表达的调控动力学。在8周龄雄性小鼠中，使用螺旋弹簧近中移动第一磨牙0、1、5或10 d。Scl表达的区域直方图和分布模式显示，Scl在受压侧牙槽骨中的表达逐渐增加，在第5天达到高峰，其显著性程度逐渐增加。第10天，牙周膜（PDL）-牙槽骨边界周围的表达恢复到对照水平。相反，Scl在张力侧的表达仅在第1天显著降低。压缩力双相调制分离的人PDL中的SOST/Scl表达，从而通过在骨细胞PDL共培养系统中的旁分泌激活上调骨细胞SOST，该系统设计用于模拟OTM。该系统不影响骨细胞中RANKL或OPG的表达，表明骨吸收途径通过RANKL/OPG信号传导以PDL依赖性和骨细胞非依赖性方式起作用。此外，sclerostin中和抗体显著减弱了由压力诱导的SOST的上调。总之，我们的研究结果提供了证据支持PDL分泌的因子，包括SOST/Scl，通过骨细胞SOST/Scl在OTM中控制牙槽骨重塑。
Sclerostin (Scl) negatively regulates bone formation and favors bone resorption. Osteocytes, the cells responsible for mechanosensing, are known as the primary source of Scl and are a key regulator of bone remodeling through the induction of receptor activator of NF-kappa B ligand (RANKL). However, the spatiotemporal patterns of Scl in response to mechanical stimuli and their regulatory mechanisms remain unknown. We investigated the regulatory dynamics of the SOST/Scl expression generated by orthodontic tooth movement (OTM) in vivo and in vitro. In 8-wk-old male mice, coil springs were used to move the first molar mesially for 0, 1, 5, or 10 d. A regional histogram and the distribution patterns of the Scl expression showed that the Scl expression in the alveolar bone was increased on the compression side and peaked on day 5, with a gradual increase in the degree of significance. On day 10, the expression around the periodontal ligament (PDL)-alveolar bone boundary returned to the control level. Conversely, the expression of Scl on the tension side was only significantly decreased on day 1. Compressive force biphasically modulated the SOST/Scl expression in the isolated human PDL and thereby upregulated osteocytic SOST via paracrine activation in an osteocyte-PDL co-culture system designed to mimic OTM. This system did not affect the RANKL or OPG expression in osteocytes, suggesting that the bone resorption pathways are acted upon in a PDL-dependent and osteocyte-independent manner through RANKL/OPG signaling. Moreover, sclerostin neutralizing antibody significantly attenuated the upregulation of SOST that was induced by compressive force. In conclusion, our results provide evidence to support that factors secreted by the PDL, including SOST/Scl, control alveolar bone remodeling through osteocytic SOST/Scl in OTM.