Abstract
Intervertebral disc (IVD) degeneration and its inflammatory microenvironment ultimately led to discogenic pain, which is thought to originate in the nucleus pulposus (NP). In this study, key genes involved in NP tissue immune infiltration in lumbar disc herniation (LDH) were identified by bioinformatic analysis. Gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The CIBERSORT algorithm was used to analyze the immune infiltration into NP tissue between the LDH and control groups. Hub genes were identified by the WGCNA R package in Bioconductor and single-cell sequencing data was analyzed using R packages. Gene expression levels were evaluated by quantitative real-time polymerase chain reaction. The immune infiltration profiles varied significantly between the LDH and control groups. Compared with control tissue, LDH tissue contained a higher proportion of regulatory T cells and macrophages, which are associated with the macrophage polarization process. The most significant module contained three hub genes and four subclusters of NP cells. Functional analysis of these genes was performed, the hub gene expression pattern was confirmed by PCR, and clinical features of the patients were investigated. Finally, we identified TGF-β and MAPK signaling pathways as crucial in this process and these pathways may provide diagnostic markers for LDH. We hypothesize that the hub genes expressed in the specific NP subclusters, along with the infiltrating macrophages play important roles in the pathogenesis of IVD degeneration and ultimately, disc herniation.
Highlights
Low back pain is a widespread and complex clinical condition affecting 70%–85% of the population worldwide
The Intervertebral disc (IVD) has been identified as an immune privilege organ because its unique structure isolates the nucleus pulposus (NP) from the immune system of the host [3], in which the annulus fibrosus (AF), cartilaginous endplate, and immunosuppressive molecular factors consist of the blood-NP barrier [4]
QRT-PCR and enzyme-linked immunosorbent assay (ELISA) were performed to verify the relationship between hub gene expression levels and clinical characteristics in lumbar disc herniation (LDH) patients
Summary
Low back pain is a widespread and complex clinical condition affecting 70%–85% of the population worldwide. Intervertebral disc (IVD) degeneration is believed to be the main cause of pain [2]. The NP triggers an immune response when the blood-NP barrier is damaged This process plays a crucial role in IVD degeneration and leads to multiple pathological processes, in which the NP loses proteoglycans and becomes more fibrotic [5]. Matrix metalloproteinases and inflammatory mediators, such as interleukin-1b (IL-1b) and tumor necrosis factor-alpha (TNF-a), are upregulated in the disc micro environment. These cytokines are produced by IVD cells and immune cells, such as macrophages and CD8 T cells [6,7,8]. The immune landscape and the role of epigenetic regulation in the pathological process of IVD degeneration remains unclear
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