Molecular mechanism of macrophage polarization regulating the cell senescence of nucleus pulposus during intervertebral disc degeneration

In orthopedics, intervertebral disc degeneration (IVDD) is a prevalent chronic condition whose cellular molecular processes are yet unclear. The objective of this research was to uncover the molecular causes of aging and identify the immunological microenvironmental alterations and immune cell infiltration in IVDD. IVDD gene datasets were obtained using GeneCards, and gene expression profiles were chosen from the Gene Expression Synthesis database (GSE244889). The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases were used to examine biological processes. The analysis of immune cell infiltration was done using CIBERSORT. To shed light on the variations in cell types among intervertebral discs with varying degrees of degeneration, single-cell analysis was carried out. Lastly, it was confirmed in vitro that important proteins and genes were expressed. At first, 10 hub genes and 58 intersecting genes were found. Major biological processes include the inflammatory response, chemokine-mediated signaling pathways, and immune response. The three main signaling mechanisms in IVDD are HIF, apoptosis, and cellular senescence. Macrophages M0, M1, M2, T cells, CD4 memory resting, NK cells, T cells regulatory (Tregs), and T cells were all markedly infiltrated in IVDD patients. According to in vitro validation, the IVDD model group had higher levels of proteins linked to the immunological microenvironment. In conclusion, immune cell infiltration-particularly macrophage infiltration, which stimulates the release of inflammatory factors that cause the inflammatory response and cellular senescence in NPCs-is linked to the primary molecular mechanisms underlying the pathogenesis of IVDD. Our research may also help direct future investigations into the senescence signaling pathway in IVDD.