microRNA-17-5p对骨髓间充质干细胞成骨向分化调控及修复根尖周骨的研究

Periapical periodontitis, as a crucial cause leading to periapical bone destruction and eventually tooth loss, is a common oral disease in clinic, which seriously threatens the patients' quality of life. The basic research and applied basic research of periapical bone destruction treatment is of great significance to endodontics. Bone marrow stromal cells (BMSCs) proved to be of tissue regenerative capacity and osteogenic differentiation potential are excellent cell sources for the regeneration of maxillofacial tissue defects. microRNA post-transcriptionally fine-tunes cellular and molecular biology events of organisms. And its expression levels are controllable, which provides a theoretical basis for the biotherapy of the disease. This project is trying to select the microRNA which is closely related to periapical bone remolding by profiling microRNA expressions of periapical bone in the diseased and physiological state; to illustrate the role of microRNA in bone remolding through inquiring its regulatory capacity and mechanisms of the osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs), which provides a theoretical basis for its treatment of bone damage; and via the animal disease models, to further probe into microRNA-17-5p, as a biotherapeutic agent, its therapeutic effect of periapical bone destruction caused by periapical periodontitis.

根尖周炎是造成牙根尖周骨质缺损并最终导致牙缺失的重要原因，是临床上常见的口腔疾病，对患者的生存质量造成了严重危害。根尖周炎骨质缺损治疗的基础及应用基础研究将对口腔内科学具有重要意义。骨髓间充质干细胞已被证明具有组织再生能力，有良好的成骨向分化潜能，是颌面部组织缺损再生的良好细胞来源。microRNA可通过转录后调控对生命体细胞分子生物学事件进行微调。microRNA自身表达水平的可控性为疾病的生物治疗提供了理论基础。本项目通过筛选调控根尖周骨修复密切相关的microRNA；通过其对骨髓间充质干细胞成骨向分化的调控能力及机制的研究，阐述microRNA在刺激成骨过程中的作用，为其对根尖周骨缺损修复的治疗提供了理论基础；并进一步通过根尖周疾病动物模型，研究microRNA-17-5p作为生物治疗因子对根尖周炎骨质缺损的治疗作用及机制，提示了根尖周骨修复再生可能的治疗新方法。

根尖周炎是造成牙根尖周骨质缺损并最终导致牙缺失的重要原因，是临床上常见的口腔疾病，对患者的生存质量造成了严重危害。根尖周炎骨质缺损治疗的基础及应用基础研究将对口腔内科学具有重要意义。骨髓间充质干细胞已被证明具有组织再生能力，有良好的成骨向分化潜能，是颌面部组织缺损再生的良好细胞来源。 microRNA 可通过转录后调控对生命体细胞分子生物学事件进行微调。microRNA 自身表达水平的可控性为疾病的生物治疗提供了理论基础。本项目成功建立了大鼠牙根尖周炎疾病动物模型；构建了大鼠牙根尖周疾病状态下及生理状态下根尖周骨组织 microRNAs 的表达模式谱；验证了microRNA-17-5p 在根尖周疾病状态下的根尖周骨组织中相对生理状态下低表达；利用小分子拟似物在根尖周组织局部提高 microRNA-17-5p 的表达水平，发现大鼠根尖周炎所致根尖周骨质吸收减少。以上研究表明microRNA-17-5p 可作为生物治疗因子对根尖周炎骨质缺损的治疗作用，提示了根尖周骨修复再生可能的治疗新方法。在体外细胞实验中，证明了microRNA-17-5p 过表达可促进骨髓间充质干细胞的成骨向分化，且这一过程可能是通过靶向作用于 TGF-β 信号通路的 SARA 蛋白, 从而影响了 TGF-β 信号通路下游的 Smads 蛋白的表达实现的，为其对根尖周骨缺损修复的治疗提供了理论基础。