SPP1 in notochord cells modulates intervertebral disc degeneration through CD44 recognition by macrophages based on single-cell transcriptome analysis

BACKGROUND: Intervertebral disc degeneration (IVDD) is a major cause of spinal disorders, often leading to chronic pain and mobility issues. Mechanical stress is a key factor in IVDD progression, but the underlying mechanisms remain unclear. In this study, we improved a rat intervertebral disc pressure model to explore how mechanical stress affects IVDD, focusing on notochord cell populations and their interactions in the degenerative process. METHODS: We developed a custom pressure device for rats, validated using imaging techniques. Following pressure application, single-cell transcriptomics was employed to analyze dynamic changes in notochord cells in both surgical and sham groups. Gene expression profiles were analyzed for immune regulation, matrix metabolism, and intercellular signaling. We also studied the SPP1 signaling pathway and its interaction with CD44. Finally, we combined Mendelian randomization and human GEO sequencing data to support our results. RESULTS: Pressure application resulted in significant structural damage and abnormal changes in matrix components, worsening over time. Single-cell analysis revealed differences in notochord cell populations between surgical and sham groups, with increased immune regulation and matrix metabolism activity. The SPP1-CD44 signaling pathway was activated in degenerated discs, especially in CD44-expressing cells, underscoring its role in matrix remodeling and inflammation. MR and human GEO sequencing data also support these ideas. CONCLUSION: This study provides insights into IVDD mechanisms, focusing on the role of the SPP1-CD44 pathway in disc degeneration. We suggest that targeting this pathway may offer potential therapeutic strategies for degenerative spinal diseases.