# Multi-omics analysis and evidence of IL1R1 as a potential biomarker for diabetes-associated intervertebral disc degeneration

## TL;DR

This study identifies IL1R1 as a potential biomarker linking diabetes and disc degeneration, offering new insights into diagnosis and treatment.

## Contribution

The novel contribution is identifying IL1R1 as a key biomarker connecting diabetes and intervertebral disc degeneration through multi-omics analysis.

## Key findings

- IL1R1 was identified as the most significant risk factor and potential diagnostic biomarker for diabetes-associated disc degeneration.
- Diabetic discs showed increased neutrophils and decreased nucleus pulposus cells, with IL1R1 highly expressed in NP subpopulations.
- A regulatory network involving IL1R1 and potential therapeutic candidate icariin was identified.

## Abstract

Low back pain (LBP), primarily driven by intervertebral disc degeneration (IDD), imposes a significant global health burden. While type 2 diabetes mellitus (T2DM) is a recognized risk factor for IDD, the shared molecular mechanisms remain incompletely characterized.

This study employed integrated bioinformatics (WGCNA, machine learning - LASSO, RF, ANN) on human T2DM and IDD transcriptomic datasets, alongside scRNA-seq analysis of diabetic mouse nucleus pulposus (NP) tissue, to identify key drivers of diabetes-associated IDD.

Bioinformatics analysis of human data identified three diagnostic biomarkers (S100A12, IL1R1, FCGR2B) and constructed a robust ANN diagnostic model (AUCs: 0.744-0.868). IL1R1 emerged as the most significant risk factor. scRNA-seq revealed altered cellular composition in diabetic discs, notably increased proportion of granulocytes (predominantly neutrophils) and decreased proportion of nucleus pulposus (NP) cells. IL1R1 was highly expressed in specific diabetes-associated NP subpopulations and showed significant positive correlation with neutrophil infiltration. Functional enrichment linked IL1R1 to inflammation, DNA repair, and immune pathways. Furthermore, we constructed a regulatory network (STAT1/STAT6-IL1R1-miRNAs-lncRNAs) and identified icariin as a potential therapeutic candidate via molecular docking.

These findings establish IL1R1 as a pivotal molecular bridge connecting T2DM and IDD, driven by neutrophil-mediated inflammation and NP cell dysfunction, offering novel diagnostic and therapeutic avenues.