炎性微环境下circBIRC6调控牙周膜干细胞成骨分化及牙周再生的机制研究

Periodontal ligament stem cells (PDLSCs) are important seed cells for periodontal tissue regeneration. However, the osteogenic differentiation and periodontal regeneration capacity of PDLSCs are significantly attenuated under the inflammatory microenvironment. Exploring the underlying molecular mechanisms is of great clinical significance for the repair and regeneration of periodontal tissues. Our preliminary studies compared the differentially expressed circRNAs between the PDLSCs from inflammatory environment and those from normal control, and found that the expression level of circBIRC6 was significantly increased following inflammatory stimulation. Downregulation of circBIRC6 promoted the osteogenic differentiation of PDLSCs in the inflammatory microenvironment. In addition, circBIRC6 might regulate prolyl hydroxylase domain-2 (PHD2) expression by absorbing miR-16-5p. Base on the above findings, this project will further elucidate the molecular mechanisms accounting for the role of circBIRC6 as the competitive endogenous RNA in regulating osteogenic differentiation and periodontal regeneration capacity of PDLSCs using in vitro inflammatory microenvironment model and rat model of periodontitis. Completion of our project will provide novel ideas for the experimental investigation and clinical translation of repairing periodontal defects.

牙周膜干细胞（PDLSCs）是实现牙周组织再生的重要种子细胞，但是其在炎症微环境下成骨分化及牙周再生能力明显下降，因此深入研究该现象的内在分子机制对于牙周组织修复再生有重要的临床意义。我们前期用高通量测序比较了炎症微环境与正常来源PDLSCs环状RNA的表达差异，发现炎症微环境下circBIRC6表达水平明显升高，抑制circBIRC6表达可促进体外炎症微环境下PDLSCs的成骨分化。初步证实了circBIRC6可能通过吸附miR-16-5p调控脯氨酸羟化酶-2（PHD2）的表达。本项目拟通过体外炎症微环境细胞模型和大鼠牙周炎骨缺损模型，进一步深入探讨circBIRC6作为竞争性内源RNA调控PDLSCs成骨分化及牙周再生的分子机制。本项目将为牙周组织缺损修复的实验研究及临床转化应用提供新思路。