长链非编码RNA n332962参与LPS调控人牙髓干细胞分化的分子机制研究

项目名称： 长链非编码RNA n332962参与LPS调控人牙髓干细胞分化的分子机制研究

项目编号： No.81470733

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 何文喜

作者单位： 中国人民解放军第四军医大学

项目金额： 73万元

中文摘要： 牙髓损伤修复的关键是牙髓干细胞（DPSCs）分化为成牙本质细胞样细胞（OBLC），但其分子机制不清。LPS是牙髓炎常见的致病因素，我们发现其可调控DPSCs分化。长链非编码RNA(lncRNA)在干细胞分化和炎性反应中均发挥重要的调控作用。我们发现lncRNA n332962能被LPS下调，同时抑制LPS调控人牙髓干细胞分化，提示其可能参与LPS调控DPSCs分化。本课题拟在前期基础上，构建lncRNA n332962过表达和沉默的DPSCs系，体内外实验研究lncRNA n332962对LPS调控DPSCs分化的影响，观察其细胞内定位，确定与其相互作用的转录因子、其调控的靶基因及其结合位点。旨在阐明lncRNA n332962参与LPS调控DPSCs向OBLC分化的分子机制，对揭示LPS在牙髓损伤修复中作用的分子机制有重要意义，为将来临床牙髓保存治疗和DPSCs组织工程应用提供新思路。

中文关键词： 牙髓干细胞；长链非编码RNA；分化；LPS

英文摘要： Dental pulp stem cells (DPSCs) differentiation into odontoblast-like cells (OBLC) is a key piont in the recovery of the injured pulp. lipopolysaccharide (LPS) is a common pathogenic factor in pulpitis. Our results showed that LPS could regulate the differentiation of DPSCs.The long noncoding RNA (lncRNA) plays an important role in the differentiation of stem cells and inflammatory response.We found that lncRNA n332962 could be downregulated by LPS and inhibited the differentiation of DPSCs mediated by LPS. It indicated that lncRNA n332962 might be involved in differentiation of DPSCs regulated by LPS. The present project will try to establish cell lines of gene overexpression or gene silencing of lncRNA n332962, to investigate the role of lncRNA n332962 in LPS-regulated differentiation of DPSCs, to observe subcellular distribution of lncRNA n332962, to clarify the interactions between transcriptional factors and lncRNA n332962, to detect the downstream target genes and related binding sites for lncRNA n332962. The objective of this project is to elucidate the molecular mechanism of involvement of lncRNA n332962 in the differentiation of DPSCs into OBLC regulated by LPS. The study would be significant for elucidation the molecular mechanism of the DPSCs differentiation into OBLC regulated by LPS during the repair of the injured pulp. It also provides a new idea for the clinical conservative treatment of vital pulp and use of DPSCs in tissue engineering in future.

英文关键词： dental pulp stem cells;long non-coding RNA;differention;LPS