Association between vertebral endplate defects and low back pain: an integrative omics study revealing the role of lipotoxicity-induced EGFR/COX-2 signalling

STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate the association between endplate defects and patient-reported outcomes and to further clarify the role of lipotoxicity-induced EGFR/COX-2 signalling in the pathogenesis of low back pain. As the hub of intervertebral discs, the metabolic status of the endplate remains poorly characterized. Investigating metabolic stress conditions and downstream biological events in the endplate may provide insights into the pathological mechanisms of endplate defects and their association with patient-reported outcomes. METHODS: Patients were classified into defect and non-defect groups based on radiographic evidence of endplate defects. Endplate cells were analyzed using lipidomics, transcriptomics, and functional assays. Outcome measures were compared between groups. Pearson's correlation was used to assess relationships among symptoms, immune-positive cells, and lipid content. Multivariate linear analysis evaluated the contribution of different variables to patient-reported symptoms. RESULTS: Preoperative VAS-Back scores (6.6 vs. 4.9, p < 0.01) and ODI scores (61.8 vs. 49.7%, p < 0.05) were significantly higher in the defect group compared to the non-defect group. Integrated analysis revealed that the defect group was characterized by lipid droplets accumulation in endplate cells and activation of the EGFR/COX2 signalling. In vivo animal studies confirmed that lipotoxicity induces endplate defects and activates EGFR/COX2 signalling. Preoperative VAS-Back and ODI scores showed positive correlations with EGFR expression (r = 0.403, p < 0.01; r = 0.466, p < 0.01) and relative lipid content (r = 0.432, p < 0.01; r = 0.358, p < 0.001) in the endplate cells. Multivariate linear analysis identified EGFR-positive cells (p = 0.010), relative triglyceride content (p = 0.049), and the presence of endplate defects (p = 0.046) as significant factors influencing preoperative VAS-Back pain. CONCLUSIONS: Patients with endplate defects reported severe symptoms and exhibited upregulation of the lipid droplet-EGFR/COX-2 pathway in endplate cells. Lipotoxicity-associated inflammatory factors significantly contribute to chronic low back pain and influence patient-reported outcomes.