Phosphatidylethanolamine Protects Nucleus Pulposus Cells From Oxidative Stress-Induced Cellular Senescence and Extracellular Matrix Degradation by Promoting Autophagy.

BACKGROUND

Intervertebral disc degeneration (IDD) is a type of musculoskeletal system diseases that prevail widely in human society, exerting a substantial economic burden on society. The extensive aggregation of senescent nucleus pulposus (NP) cells within the discs is a significant characteristic of lumbar degenerative alterations. Exploring the underlying mechanisms of NP cell senescence and developing strategies to retard cell senescence are anticipated to become effective approaches for the treatment of IDD.

OBJECTIVE

The study aims to investigate the effects of phosphatidylethanolamine (PE) on autophagic activity, cellular senescence, as well as IDD and dedicated to forging an evidence chain that interconnects IDD, the senescence of NP cells, the autophagic malfunction of NP cells, and the aberrant PE content in NP cells of the advanced-stage group. The resultant outcomes will furnish a theoretical underpinning for the biological prophylaxis and treatment of IDD.

METHODS

Oxidative stress-induced NP cells senescence is a fundamental characteristic of IDD. To obtain a understanding of the metabolite profile changes in NP cells under stress conditions, Liquid Chromatograph/Mass Spectrometer-based untargeted metabolomics (LC/MS) analysis was utilized in this study. Upon analysis, the distinctive metabolite, PE, which decreased in content in advanced-stage cells, was identified. In this study, Tert-Butyl hydroperoxide (TBHP) was selected as the oxidant to construct an in vitro cellular oxidation model. Methods such as immunofluorescence, immunohistochemistry, Western blotting, and transmission electron microscopy were employed to explore the effects of PE on the senescence of NP cells, the degradation of the extracellular matrix (ECM), and the autophagy of NP cells under stress conditions.

RESULTS

The administration of PE effectively attenuates TBHP-induced cellular senescence and ECM degradation in NP tissue, primarily by stimulating autophagy. Nonetheless, this restorative effect is hindered by chloroquine (CQ), a lysosomal alkalizing agent.

CONCLUSIONS

In our study, a series of experiments established a conclusive evidential chain linking IDD, senescence of NP cells, impaired cellular autophagy activity, and abnormal PE content within advanced-stage NP cells. The unique function of PE in promoting NP cells autophagy, thereby delaying cellular senescence, restoring cellular homeostasis, and ECM, suggests its potential as an effective drug for the clinical treatment of IDD.