PGE2在拔牙创愈合骨改建中的作用及机理研究

Inflammation is the main reason to cause the resorption of alveolar ridge after tooth extraction. Our previous studies showed the increased expression of TNF-α and IFN-γ as well as the number of osteoclasts in the early stage of post-extraction, however, reduced production of pro-inflammatory factors could not rescue the bone loss after tooth extraction, which made us reconsider the role of inflammatory factors in the bone reconstruction . PGE2, as an important inflammatory mediator after injury, could affect the maturation of osteoclasts by regulating the differentiation of T cells. Besides, it also play a role in the proliferation and differentiation of osteoblasts. Based on the previous studies, our project aims to find out the expression of E-prostanoid, the receptor of PGE2 on the differentiation of Th0 cell and osteoblasts by the methods of FCM and RT-PCR; Besides, the mechanism of PGE2 on the proliferation and differentiation of osteoblasts are explored by FCM and MTT. Differentiation of Th0 to Treg or Th17 with the induction of PGE2 is also explored as well as the underlying mechanisms. This project would not only lay solid foundation to for prevention and treatment of alveolar bone loss, but also provide new insight in clinic approaches.

拔牙创后局部炎症反应是导致剩余牙槽嵴吸收的主要原因。本课题前期研究建立了大鼠拔牙创愈合模型，发现拔牙创愈合初期TNF-α、IFN-γ表达升高，破骨细胞数量增加；但单纯降低炎症因子水平并不能改善骨量的丧失，使申请人重新审视炎症因子在骨改建中的作用。PGE2作为组织损伤后产生的重要炎症介质，不仅可影响T细胞介导的破骨细胞的激活，同时也在成骨细胞的增殖分化扮演重要角色。基于以上研究基础，本研究拟采用流式细胞术、RT-PCR检测PGE2受体EP1-4在成骨细胞、Th0细胞表面的表达与分布；观察不同浓度的PGE2对成骨细胞增殖分化的影响以及可能的受体途径；流式及定量PCR观察PGE2对Th0细胞向Treg及Th17细胞分化的调节及作用机制。通过对PGE2受体的研究和筛选，探索将PGE2受体作为治疗靶点，预防和减少牙槽嵴骨质丧失，以期为临床保留剩余牙槽嵴骨量提供新的治疗思路和实验依据。