Sclerostin Promotes Bone Remodeling in the Process of Tooth Movement.

Tooth movement is a biological process of bone remodeling induced by mechanical force. Sclerostin secreted by osteocytes is mechanosensory and important in bone remodeling. However, little is known regarding the role of sclerostin in tooth movement. In this study, models of experimental tooth movement were established in rats and mice. Sclerostin expression was investigated with immunohistochemistry staining, and osteoclastic activity was analyzed with tartrate-resistant acid phosphatase (TRAP) staining. MLO-Y4 osteocyte-like cells underwent uniaxial compression and tension stress or were cultured in hypoxia conditions. Expression of sclerostin was assessed by RT-qPCR and ELISA. MLO-Y4 cells were cultured with recombinant human sclerostin (rhSCL) interference and then co-cultured with RAW264.7 osteoclast precursor cells. Expressions of RANKL and OPG were analyzed by RT-qPCR, and osteoclastic activity was assessed by TRAP staining. During tooth movement, sclerostin was expressed differently in compression and tension sites. In SOST knock-out mice, there were significantly fewer TRAP-positive cells than in WT mice during tooth movement in compression sites. In-vitro studies showed that the expression of sclerostin in MLO-Y4 osteocyte-like cells was not different under a uniaxial compression and tension force, whereas hypoxia conditions significantly increased sclerostin expression in MLO-Y4 cells. rhSCL interference increased the expression of RANKL and the RANKL/OPG ratio in MLO-Y4 cells and the osteoclastic induction ability of MLO-Y4 cells in experimental osteocyte-osteoclast co-culture. These data suggest that sclerostin plays an important role in the bone remodeling of tooth movement.

牙齿移动是由机械力诱导的骨重塑的生物学过程。骨细胞分泌的硬骨素具有机械感知作用，在骨重塑中起重要作用。然而，关于硬骨素在牙齿移动中的作用知之甚少。在本研究中，在大鼠和小鼠中建立了实验性牙齿移动模型。通过免疫组织化学染色研究硬骨素的表达，并通过抗酒石酸酸性磷酸酶（TRAP）染色分析破骨细胞活性。MLO - Y4类骨细胞样细胞承受单轴压缩和拉伸应力或在缺氧条件下培养。通过实时定量聚合酶链反应（RT - qPCR）和酶联免疫吸附测定（ELISA）评估硬骨素的表达。MLO - Y4细胞在重组人硬骨素（rhSCL）干扰下培养，然后与RAW264.7破骨细胞前体细胞共培养。通过RT - qPCR分析核因子κB受体活化因子配体（RANKL）和骨保护素（OPG）的表达，并通过TRAP染色评估破骨细胞活性。在牙齿移动过程中，硬骨素在受压和受拉部位的表达不同。在硬骨素基因敲除（SOST knock - out）小鼠中，在受压部位牙齿移动期间，抗酒石酸酸性磷酸酶阳性细胞明显少于野生型（WT）小鼠。体外研究表明，在单轴压缩和拉伸力作用下，MLO - Y4类骨细胞样细胞中硬骨素的表达没有差异，而缺氧条件显著增加了MLO - Y4细胞中硬骨素的表达。重组人硬骨素干扰增加了MLO - Y4细胞中核因子κB受体活化因子配体的表达以及核因子κB受体活化因子配体与骨保护素的比值，并增加了在实验性骨细胞 - 破骨细胞共培养中MLO - Y4细胞的破骨诱导能力。这些数据表明硬骨素在牙齿移动的骨重塑中起重要作用。