1 Department of Orthodontics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
2 Department of Orthodontics, Okayama University Hospital, Okayama, Japan.
J Dent Res. 2018 Nov;97(12):1374-1382. doi: 10.1177/0022034518771331. Epub 2018 Jun 4.
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-κB 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.
骨硬化蛋白（Scl）负向调节骨形成并有利于骨吸收。骨细胞作为机械感受器的细胞，被认为是 Scl 的主要来源，通过诱导核因子-κB 受体激活剂配体（RANKL）来调节骨重塑。然而，Scl 对机械刺激的时空模式及其调节机制尚不清楚。我们研究了体内和体外正畸牙齿移动（OTM）诱导的 SOST/Scl 表达的调节动态。在 8 周龄雄性小鼠中，使用螺旋弹簧将第一磨牙向近中移动 0、1、5 或 10 天。区域直方图和 Scl 表达的分布模式表明，牙槽骨的 Scl 表达在受压侧增加，并在第 5 天达到峰值，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，张力侧的 Scl 表达仅在第 1 天显著降低。压缩力在体外分离的人牙周膜中双相调节 SOST/Scl 表达，并通过设计模拟 OTM 的成骨细胞-PDL 共培养系统中的旁分泌激活来上调成骨细胞 SOST。该系统不会影响成骨细胞中 RANKL 或 OPG 的表达，这表明通过 RANKL/OPG 信号，骨吸收途径在 PDL 依赖性和骨细胞独立性方式下作用于骨细胞。此外，骨硬化蛋白中和抗体显著减弱了压缩力诱导的 SOST 上调。总之，我们的结果提供了证据支持 PDL 分泌的因子，包括 SOST/Scl，通过 OTM 中的成骨细胞 SOST/Scl 控制牙槽骨重塑。
