Glycine-Serine-Threonine Metabolic Axis Delays Intervertebral Disc Degeneration through Antioxidant Effects: An Imaging and Metabonomics Study

甘氨酸-丝氨酸-苏氨酸代谢轴通过抗氧化作用延缓椎间盘退变:一项影像学和代谢组学研究

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作者:Xiaolin Wu, Chang Liu, Shuai Yang, Nana Shen, Yan Wang, Youfu Zhu, Zhaoyang Guo, Shang-You Yang, Dongming Xing, Houxi Li, Zhu Guo, Bohua Chen, Hongfei Xiang

Abstract

Although intervertebral disc degeneration (IDD) can be described as different stages of change through biological methods, this long and complex process cannot be defined in stages by single or simple combination of biological techniques. Under the background of the development of nuclear magnetic resonance (NMR) technology and the emerging metabonomics, we based on animal models and expanded to the study of clinical human degeneration models. The characteristics of different stages of IDD were analyzed by omics. Omics imaging combined with histology, cytology, and proteomics was used for screening of the intervertebral disc (IVD) of research subjects. Furthermore, mass spectrometry nontargeted metabolomics was used to explore profile of metabolites at different stages of the IDD process, to determine differential metabolic pathways and metabolites. NMR spectroscopy was used to qualitatively and quantitatively identify markers of degeneration. NMR was combined with mass spectrometry metabolomics to explore metabolic pathways. Metabolic pathways were determined through protein molecular biology and histocytology of the different groups. Distinguishing advantages of magnetic resonance spectroscopy (MRS) for analysis of metabolites and effective reflection of structural integrity and water molecule metabolism through diffusion tensor imaging (DTI) were further used to verify the macrometabolism profile during degeneration. A corresponding model of in vitro metabolomics and in vivo omics imaging was established. The findings of this study show that a series of metabolic pathways associated with the glycine-serine-threonine (Gly-Ser-Thr) metabolic axis affects carbohydrate patterns and energy utilization efficiency and ultimately delays disc degeneration through antioxidant effects.

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