Identification and Experimental Validation of PANoptosis Key Genes for Constructing a PANoptosis Risk Diagnostic Model in Intervertebral Disc Degeneration

BACKGROUND: Intervertebral disc degeneration (IDD) represents a significant health concern globally. This study aimed to identify the PANoptosis key genes (PKGs) associated with IDD and construct a risk diagnosis model METHODS: Single-cell sequencing, machine learning algorithms, and LASSO regression were employed to identify PKGs and develop a risk model. The expression of identified PKGs was validated in human IDD clinical tissues using qRT-PCR, Western blot, and immunohistochemistry. The therapeutic effect of ACSBG1 knockdown was further evaluated in a rat IDD model by histological analysis. RESULTS: The seven most representative PKGs of IDD (ACSBG1, FXYD1, APCS, CEACAM1, ERAP2, ABL1, and FZD3) were identified. Utilizing these seven PKGs, an IDD PANoptosis risk diagnosis model was constructed and validated. Immune infiltration analysis revealed a significant association between the PANoptosis risk of IDD and immune cells, particularly neutrophils. Clinical validation confirmed that ACSBG1, FXYD1, APCS, and CEACAM1 were upregulated, while ERAP2, ABL1, and FZD3 were downregulated in nucleus pulposus tissues of IDD patients. In a rat model, ACSBG1 knockdown markedly attenuated disc degeneration, preserving disc structure and increasing proteoglycan content. CONCLUSION: This study established an IDD PANoptosis risk diagnosis model and demonstrated that targeting ACSBG1 exerted therapeutic effects in vivo, providing new insights into the diagnosis and treatment of IDD.