TLR4/TLR5信号优势调控Runx2在成骨细胞分化过程中的作用与关键机制研究

The bone metabolism is determined by the dynamic balance between the osteoclast-driven bone resorption and the osteoblast-driven bone formation, and the latter plays a key role in this procedure. Even though osteoblast highly expresses a variety of TLRs, the mechanism of TLRs signal on osteoblast differentiation is unclear. Moreover, the relationship between TLRs signal and osteoblast differentiation signal still remains unknown. Our previous studies had found that TLR4 and TLR5 signals display different influences on osteoblast differentiation through regulating osteogenic differentiation factor Runx2. However, the underlying mechanism is unclear. In this research, we will try to further elucidate the molecular mechanism of TLR4 and TLR5 regulating osteoblast differentiation by finding the key targets. Furthermore, we will try to reveal the communicating correlation between TLR4 /TLR5 signal and Runx2.

成骨细胞主导的骨形成和破骨细胞主导的骨吸收之间的动态平衡是决定骨代谢稳定的关键环节，其中，成骨细胞分化模式发挥着主导作用。尽管介导天然免疫及特异性免疫应答的TLRs在成骨细胞高表达，但TLRs信号对成骨细胞分化的调控机制尚不清楚，更缺乏对TLRs信号与成骨细胞分化信号之间信息传递规律的深刻认识。我们前期研究发现，TLR4与TLR5信号对成骨细胞前体分化具有不同的调控作用，成骨分化因子Runx2可能是其关键调控靶点，而TLR4和TLR5信号是如何调控Runx2的，及在成骨细胞前体分化过程中的作用尚不明确。因此，本项目拟在此基础上，进一步深入探讨TLR4、TLR5信号调控成骨细胞分化及功能的具体分子机制，揭示TLR4、TLR5信号与Runx2之间通讯联系的规律。

成骨细胞主导的骨形成和破骨细胞主导的骨吸收之间的动态平衡是决定骨代谢稳定的关键环节，其中，成骨细胞分化模式发挥着主导作用。我们前期研究发现，TLR4与TLR5配基刺激活化的TLRs信号对成骨细胞分化存在差异性调控，本项目试图从分子水平寻找出这种差异调控的机制。研究过程中我们发现TLR4促进成骨细胞分泌产生的IL-6可能对成骨细胞分化有重要影响， 提示细胞因子可能在成骨分化调控中起着重要作用。下一步将围绕此发现展开细胞因子调控成骨细胞分化机制的研究，以期为骨代谢调控提供新的理论依据。