炎症微环境中长链非编码RNA-MIR31HG调控骨髓间充质干细胞成骨分化的研究

骨缺损修复引起的炎症反应在骨改建中发挥重要作用。虽然骨髓间充质干细胞（BMSCs）是组织工程中修复骨缺损的理想种子细胞之一，但炎症微环境对BMSCs成骨分化的影响及分子机制尚不清楚。已知长链非编码RNA（lncRNA）在干细胞分化中起重要作用，但其在炎症微环境下如何调控干细胞成骨分化尚未见报道。本项目前期研究表明，炎症因子可上调BMSCs中lncRNA-MIR31HG的表达；敲低MIR31HG不仅促进干细胞成骨分化，还同时抑制炎症反应关键通路NF-κB活性。因此，我们推测MIR31HG与NF-κB之间存在相互调控环路，并可能影响炎症环境下干细胞成骨分化。本研究拟通过体外细胞学，分子生物学和动物体内实验，明确MIR31HG在炎症微环境中对BMSCs成骨的影响，并深入阐明MIR31HG与NF-κB间相互调控的分子机制，探索利用lncRNA为药物靶点实现拮抗炎症因子进而高效促进干细胞成骨分化。

The bone renewal process is usually complicated by inflammatory reaction. Although bone marrow mesenchymal stem cells (BMSCs) is one of the ideal seed cells of tissue engineering for repairing bone loss，the mechanism for the inhibition of BMSC osteoblast differentiation under inflammatory condition remains unclear. Several studies indicated long non-coding RNAs (lncRNAs) are important in BMSC osteogenesis, but whether lncRNAs are involved in inflammatory inhibition of bone formation remains unknown. In this study, we confirmed that lncRNA-MIR31HG was upregulated by the stimulation of inflammatory cytokines. In turn, MIR31HG regulated the NF-κB activity and knockdown of MIR31HG significantly promoted BMSC osteogenic differentiation. Thus, we propose the regulatory circuitry between MIR31HG and NF-κB may affect BMSC osteoblast differentiation under inflammatory condition. This project is conducive to confirm the role of MIR31HG in osteoblast differentiation of BMSCs under inflammatory condition in vitro and in vivo, and determine the molecular mechanism of the regulatory loop between MIR31HG and NF-κB signaling pathway. This project will be helpful to verify the value of lncRNA as effective target molecular for enhancing bone regeneration under inflammatory condition, and will benefit the clinical translation of bone tissue engineering based on BMSCs.