miRNA21通过RANKL影响小鼠正畸牙齿移动的机制研究

The regulation mechanism of orthodontic bone remodeling is complex, and OPG/RANKL/RANK axis is the key control factor. In recently, the effects of systemic factors have been paid attention to. miRNA21 plays a central role in regulating host immune system and mature process of osteoclast. Until now, how miRNA21 participate orthodontic tooth movement and bone remodeling is unclear. We found orthodontic tooth movement in miRNA21 knockout mice was significantly slower than that in wild type mice. After further investigating, we found RANKL secretion was insufficient in miRNA21 knockout mice, but OPG, RANK and Th1/Th2/Th17/Treg ratio have no obvious changes. These results suggested that the decreased capability of tooth movement was link to the insufficient of RANKL secretion in miRNA21 knockout mice. Based on our previous study, the proposal will investigate the different pattern of wild type mice and miRNA21 knock during orthodontic tooth movement, and found the mechanism of miRNA21 influence OPG/RANKL/RANK. We try to reveal the important role of miRNA21 in bone modeling and orthodontic tooth movement. The results will help to understand how host systemic factors on effect orthodontic tooth movement, and will provide basic knowledge to understanding the relationship between miRNAs and bone remodeling.

正畸骨改建的调控机制复杂，其中OPG/RANKL/RANK轴为核心调控因素，近年来全身因素的影响受到重视。miRNA21在免疫调节中发挥重要作用并与破骨细胞成熟相关，但如何参与骨改建尚不明确。申请人前期研究发现miRNA21敲除鼠正畸牙移动速度明显低于野生型小鼠，RANKL分泌量不足，OPG、RANK及Th1/Th2/Th17/Treg比例无明显变化。将野生型小鼠脾脏细胞回输后可显著增加敲除鼠RANKL量及正畸牙移动速度，提示miRNA21敲除引起的RANKL降低是影响其正畸牙移动的关键因素。本项目拟在前期研究基础上比较野生型及miRNA21敲除鼠正畸牙移动模式差异，研究miRNA21对OPG/RANKL/RANK轴影响规律，发现miRNA21促进RANKL分泌的相关机制。研究结果对揭示miRNA21在骨免疫及正畸牙移动中的重要作用提供依据，为了解影响正畸牙移动的全身因素提供重要参考。

随着社会发展，人们对美的需求渐渐提高，越来越多的人开始寻求正畸治疗，以期获得健康整齐的牙齿。正畸骨改建的调控机制复杂，尤其是全身因素对正畸牙齿移动的影响还研究较少。骨改建是正畸牙齿移动的生物学基础，骨改建中成骨破骨的动态平衡是牙齿发生健康移动的前提和基础。在骨改建中，OPG/RANKL/RANK轴为核心调控因素。miRNA21在免疫调节中发挥重要作用并与破骨细胞成熟相关，但如何参与骨改建尚不明确。本课题在前期研究中发现miRNA21敲除鼠正畸牙移动速度明显低于野生型小鼠，RANKL分泌量不足，OPG、RANK及Th1/Th2/Th17/Treg比例无明显变化。将野生型小鼠脾脏细胞回输后可显著增加敲除鼠RANKL量及正畸牙移动速度，提示miRNA21敲除引起的RANKL降低是影响其正畸牙移动的关键因素。本项目在进一步研究中，系统研究了miRNA21在正畸牙齿移动中的调控作用，主要发现：1.miRNA21敲除抑制小鼠破骨细胞及正畸牙齿移动；2.miRNA21缺乏会引起小鼠全身RANKL分泌水平下降；3.miRNA21可以促进活化的T细胞分泌RANKL，当miRNA21缺乏时，活化T细胞分泌RANKL水平下降；4。回输T细胞可以部分增加miRNA21敲除小鼠牙齿移动速度以及破骨细胞的生成。通过本研究我们发现了miRNA21可以通过调节T细胞中RANKL/OPG平衡进而影响小鼠正畸牙齿移动。本项目比较了野生型及miRNA21敲除鼠正畸牙移动模式差异，研究了miRNA21对OPG/RANKL/RANK轴影响规律，发现了miRNA21促进RANKL分泌的相关机制。研究结果对揭示miRNA21在骨免疫及正畸牙移动中的重要作用提供依据，为了解影响正畸牙移动的全身因素提供重要参考，并为将来小分子RNA靶向干预骨改建调控正畸牙齿移动提供重要理论基础。通过本课题研究，发表基金标注相关论文11篇，总影响因子41.7。