Wang Lulu, Zhou Zhifei, Chen Yujiang, Yuan Shuai, Du Yang, Ju Xinke, Wu Lizheng, Wang Xiaojing
1 State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases, and Shaanxi Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University , Xi'an, China .
2 Department of Stomatology, Affiliated Hospital of Logistic University of People's Armed Police Forces , Tianjin, China .
Stem Cells Dev. 2017 Aug 15;26(16):1186-1198. doi: 10.1089/scd.2017.0033. Epub 2017 Jun 26.
The physiological root resorption of deciduous teeth is a normal phenomenon, but the mechanisms underlying this process are still unclear. In this study, deciduous dental pulp stem cells (DDPSCs) and permanent dental pulp stem cells (DPSCs) were derived from deciduous teeth and normal permanent teeth at different stages of resorption. In the middle stage of root resorption, DDPSCs exhibited an increase in the ability to induce osteoclast differentiation. Activation of the alpha 7 nicotinic acetylcholine receptor (α7 nAChR) by secretory mammalian Ly-6 urokinase-type plasminogen activator receptor-associated protein 1 (SLURP-1) caused a significant increase in the expression levels of NF-κB, receptor activator of nuclear factor-kappa B ligand (RANKL), and the ratio of RANKL/osteoprotegerin (OPG). These effects were inhibited by alpha-bungarotoxin (α-BTX). Furthermore, the expression levels of RANKL/OPG were significantly reduced following inhibition of NF-κB. High-strength, dynamic positive pressure increased the expression of SLURP-1 and α7 nAChR in DDPSCs in the stable stage. These data indicated that mechanical stress stimulated the expression of SLURP-1 and α7 nAChR in DDPSCs. Additionally, SLURP-1 activated α7 nAChR, thereby upregulating the expression of NF-κB and enhancing its activity, thus regulating RANKL/OPG expression and affecting the ability of DDPSCs to influence osteoclastogenesis, which likely enhances root resorption and leads to the physiological loss of deciduous teeth.
乳牙的生理性牙根吸收是一种正常现象,但其发生过程的机制仍不清楚。在本研究中,乳牙牙髓干细胞(DDPSCs)和恒牙牙髓干细胞(DPSCs)分别来源于处于不同吸收阶段的乳牙和正常恒牙。在牙根吸收的中期,DDPSCs诱导破骨细胞分化的能力增强。分泌型哺乳动物Ly-6尿激酶型纤溶酶原激活物受体相关蛋白1(SLURP-1)激活α7烟碱型乙酰胆碱受体(α7 nAChR),导致核因子κB(NF-κB)、核因子κB受体激活剂配体(RANKL)的表达水平以及RANKL/骨保护素(OPG)的比值显著升高。这些作用被α-银环蛇毒素(α-BTX)抑制。此外,抑制NF-κB后,RANKL/OPG的表达水平显著降低。高强度动态正压增加了稳定期DDPSCs中SLURP-1和α7 nAChR的表达。这些数据表明机械应力刺激了DDPSCs中SLURP-1和α7 nAChR的表达。此外,SLURP-1激活α7 nAChR,从而上调NF-κB的表达并增强其活性,进而调节RANKL/OPG的表达,影响DDPSCs影响破骨细胞生成的能力,这可能会增强牙根吸收并导致乳牙的生理性脱落。