METHODS: RNA sequencing and metabolomics experiments were combined to evaluate the primary nucleus pulposus and screen key targets under mechanical biological stimulation. Additionally, small molecules work in vitro were used to confirm the target regulatory effect and investigate the mechanism. In vivo, treatment effects were validated using a rat caudal vertebrae compression model.
RESULTS: Our research results revealed that by activating TRPC6, hyperforin, a herbaceous extract can rescue the inflammatory phenotype caused by the stiff microenvironment, hence reducing intervertebral disc degeneration (IDD). Mechanically, it activates mitochondrial fission to inhibit PFKFB3.
CONCLUSIONS: In summary, this study reveals the important bridging role of TRPC6 between mechanical stiffness, metabolism, and inflammation in the context of nucleus pulposus degeneration. TRPC6 activation with hyperforin may become a promising treatment for IDD.
方法:将RNA测序和代谢组学实验结合起来评估初级髓核,并在机械生物刺激下筛选关键靶标。此外,利用小分子在体外的作用来确认靶点的调节作用并探讨其作用机制。在体内,使用大鼠尾椎压迫模型验证治疗效果。
结果:我们的研究结果表明,通过激活TRPC6,hyperforin,草本提取物可以挽救由僵硬的微环境引起的炎症表型,从而减少椎间盘退变(IDD)。机械上,它激活线粒体裂变以抑制PFKFB3。
结论:总之,这项研究揭示了TRPC6在机械刚度之间的重要桥梁作用,新陈代谢,和炎症在髓核变性的背景下。用hyperforin激活TRPC6可能成为IDD的有希望的治疗方法。