Integrating Bulk RNA and Single-Cell RNA Sequencing Identifies and Validates Lactylation-Related Signatures for Intervertebral Disc Degeneration.

Glycolysis-related lactylation has gained wide attention for regulating various cellular functions and diseases. Nevertheless, its intricate involvement in intervertebral disc degeneration (IVDD) is not yet fully understood. In this study, we unrevealed the intricate association between elevated lactylation levels and the development of IVDD. Subsequently, we harvested the lactylation-related genes (LRGs) and systematically analysed the expression levels of these genes to establish a gene signature related to IVDD through multiple bulk RNA sequencing data. Six hub LRGs were determined and closely associated with the increased severity of IVDD. Among the six genes, CBX3 was the most upregulated in both in vivo and in vitro experiments. Furthermore, molecular docking identified atosiban acetate as a specific inhibitor for CBX3, and inhibiting the expression of CBX3 using atosiban acetate significantly repressed the glycolysis activity and global lactylation level, thus alleviating the progression of IVDD. In conclusion, the lactylation correlates positively with IVDD and the LRG signature could be used as a biomarker for the effective clinical treatment of IVDD. CBX3 emerged as one of the key LRGs in IVDD, and atosiban acetate, as a specific inhibitor for CBX3, may be a promising therapeutic candidate for IVDD by affecting lactylation.