长链非编码RNA-SNHG5调控正畸牙根吸收的作用及机制研究

牙根吸收是正畸治疗最常见的并发症，其根本原因在于正畸力下牙周膜细胞的成/破牙骨质代谢失衡，寻找这一平衡的核心调控分子是减少牙根吸收的关键。课题组前期发现压力下牙周膜细胞中长链非编码RNA-SNHG5表达下调，伴随成牙骨质分化抑制，并初步揭示YY1转录因子对SNHG5存在调控功能。本研究拟探索YY1/SNHG5信号介导压应力调控成/破牙骨质分化的作用和机制。拟利用大鼠牙齿移动模型和静压力模型明确在压力下牙周膜组织中YY1和SNHG5的表型，通过敲低和过表达YY1/SNHG5揭示其对成/破牙骨质分化的调控作用，结合生物信息学分析与生物功能验证，解析SNHG5调控miR-132/GDF5诱导成牙骨质分化、调控CEBPβ/RANKL诱导破牙骨质分化的分子机制，并构建SNHG5基因敲除小鼠验证SNHG5在正畸牙根吸收中的功能。本研究将拓展对正畸牙根吸收分子机制的认知，为减少正畸牙根吸收提供理论基础。

Root resorption is one of the most common complications in orthodontic treatment, which results from the imbalance of cementoblast and cementoclast differentiation. It is important to investigate the key regulatory molecules of cementum remodeling for reducing the orthodontically induced root resorption. The preliminary results of our research group discovered that mechanical compressive force significantly downregulated the expression of long non-coding RNA SNHG5 in periodontal ligament cells with the inhibition of cementogenesis, and the level of SNHG5 was regulated by the upstream transcription factor YY1. Based on the preliminary results, this study aims to investigate the role and mechanism of YY1 and SNHG5 in cementoblast and cementoclast differentiation under compressive force. We will determine the expression levels of YY1 and SNHG5 in periodontal ligament tissue under compressive force using rat tooth movement model in vivo and static compressive force model in vitro. We will then reveal the regulatory role of YY1 and SNHG5 in cementoblast and cementoclast differentiation by gain-of-function and loss-of-function assays. According to the high-throughput sequencing data and molecular biology assays, we will investigate the underlying mechanism of SNHG5 regulating cementoblast differentiation via miR-132/GDF5, and regulating cementoclast differentiation via CEBPβ/RANKL. Further, we will use SNHG5 knockout mice to verify the regulatory function of SNHG5 in root resorption. This study will be helpful to expand the cognition of molecular mechanism of orthodontically induced root resorption, and develop the potential strategy to reduce orthodontically induced root resorption.