软骨细胞Ephrin B2/ALK1/Smad1/5/8信号轴介导创伤性骨关节炎及骨健口服液干预的机制研究

创伤性骨关节炎（TOA）是常见的关节创伤后遗症，我们前期高通量测序显示TOA软骨加速退变与Ephrin-Eph系统相关，TOA软骨细胞中Ephrin B2表达减少，抑制软骨细胞Ephrin B2可活化ALK1/Smad1/5/8信号，提示TOA软骨加速退变可能与Ephrin B2/ALK1/Smad1/5/8信号轴相关。TOA发展过程属气滞血瘀兼肝肾亏虚的虚实夹杂证，适用“补肾活血通络”功效的骨健口服液治疗，前期发现骨健口服液能延缓TOA软骨退变，并升高Ephrin B2水平。因此，Ephrin-Eph系统介导TOA软骨加速退变及骨健口服液有效延缓TOA软骨退变的作用机制值得深入研究。本项目拟用敲基因小鼠为工具，结合病理组织学、分子生物学、蛋白组学等研究方法，揭示软骨细胞Ephrin B2/ALK1/Smad1/5/8信号轴介导TOA及骨健口服液干预的作用机制。

Traumatic osteoarthritis (TOA) is a common sequelae of joint trauma. Previous high-throughput sequencing data indicated that accelerated cartilage degeneration in TOA was associated with the ephrin-Eph system. The Ephrin B2 expression was decreased in TOA chondrocytes, and inhibition of Ephrin B2 activated ALK1/Smad1/5/8 signal axis, which suggesting that the accelerated degeneration of post-traumatic cartilage may be related to Ephrin B2/ALK1/Smad1/5/8 signal axis. TOA is a syndrome of Qi stagnation and blood stasis combined with deficiency of liver and kidney. It is suitable for the treatment of Gujian Oral Liquid with the effect of "tonifying kidney and activating blood circulation". It was previously found that Gujian Oral Liquid could delay the degeneration of TOA cartilage and increase the level of Ephrin B2. .Therefore, the mechanisms of Ephrin-Eph system mediating TOA cartilage degeneration and Gujian oral liquid effectively delaying TOA cartilage degeneration is worth for further study. In this study, we planned to use gene knockout mice as tools, combined with histopathology, molecular biology, proteomics and other research methods, to reveal the mechanism of Ephrin B2/ALK1/Smad1/5/8 signal axis in chondrocyte mediated traumatic osteoarthritis and Gujian oral liquid intervention.