Deciphering the regulatory mechanism and therapeutic potential of ECM degradation in intervertebral disc degeneration via multi-omics integration

BackgroundIntervertebral disc degeneration (IVDD) is a major cause of chronic low back pain, characterized not only by extracellular matrix (ECM) degradation but also by a chronic low-grade inflammatory response. The crosstalk between immune microenvironment dysregulation and protease-driven ECM breakdown remains poorly understood, hindering the development of targeted therapies.MethodsWe integrated multiple transcriptomic datasets to map the landscape of ECM-degrading proteases in IVDD.

Machine learning algorithms (LASSO, Random Forest, SVM) were employed to identify key regulatory genes. Their association with immune cell infiltration and inflammatory pathways was investigated.

A diagnostic ridge regression model was constructed, and molecular docking was performed to screen for potential therapeutics. The top candidate, pravastatin sodium, was validated in vitro and in vivo for its effects on ECM preservation and inflammation modulation.ResultsMMP3 and ADAMTS1 were identified as core genes driving ECM degradation, and their expression was strongly correlated with the abundance of pro-inflammatory immune cells and activation of inflammatory pathways.

The model based on these genes effectively distinguished degenerated discs.