Enzymic and Immunological Activity in the Intervertebral Disc

Naylor, A.; Happey, F.; Turner, Robert L.; Shentall, R.D.; West, David C.; Richardson, Colin

doi:10.1016/s0030-5898(20)31199-8

Cited by 55 publications

(9 citation statements)

References 4 publications

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“…The nucleus pulposus (NP) is the largest avascular organ which is located at the center intervertebral disc (IVD). The unique anatomical structure isolates NP from the host immune system and therefore, NP has been identified as an immune privilege organ by Naylar et al since 1975 [ 6 ]. However, the disruption of the NP-blood barrier due to annulus fibrosus rupture leads to exposure of NP to the host and triggers numerous immune cells infiltration and immune response.…”

Section: Introductionmentioning

confidence: 99%

Development of a Novel Inflammatory-Associated Gene Signature and Immune Infiltration Patterns in Intervertebral Disc Degeneration

Lan

Guo

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Both inflammatory factors and immune response play important roles in the pathogenesis of intervertebral disc degeneration (IDD). However, a comprehensive analysis of interaction between inflammatory response-associated genes (IRGs) and immune microenvironment in patients with IDD remains lacking. Hence, the current research is aimed at investigating the correlations between IRG signatures and immune cells in the progression of IDD. Methods. The expression profiles (GSE27494 and GSE41883) and IRGs were downloaded from the Gene Expression Omnibus (GEO) database and Molecular Signature Database (MSigDB), respectively. Weighted gene coexpression network analysis (WGCNA) and differential expression analysis were used to identify the pivotal modules and common differentially expressed genes (DEGs) associated with IDD. Subsequently, we retrieved differentially expressed IRGs (DE-IRGs) by intersecting IRGs and DEGs for enrichment analysis. Next, LASSO regression analyses were performed to screen optimal marker genes for IDD prediction. Additionally, we validated differences DE-IRGs between IDD patients and controls in GSE150408. Finally, the infiltration alteration of immune cells was evaluated by the CIBERSORT, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. Results. A total of 10 upregulated differentially expressed inflammatory genes were identified that were obviously related to progression of IDD. Functional analysis results revealed that DE-IRGs were mainly enriched in signaling pathways TNF, IL-17, NOD-like receptor, and NF-kappa B pathway. A five-gene signature that consisted of IL-1β, LIF, LYN, NAMPT, and SLC7A2 was constructed by the LASSO Cox regression. IL1B, LYN, and NAMPT were further validated as optimal candidate genes in the pathophysiology of IDD. In addition, there was a remarkable immune cell infiltration difference between the healthy and IDD groups. The proportions for dendritic cells activated, mast cells activated, and neutrophils in the IDD group were significantly higher than those in the normal group, while the proportion of some cells was lower than that of the normal group, such as T cell CD4 memory resting, NK cells activated, and macrophage M0. Furthermore, correlation analysis indicated IL-1β, LYN, and NAMPT were closely implicated with immune cell infiltration in IDD development. Conclusions. We explored an association between inflammatory response-associated signature and immune infiltration in IDD and validated that IL-1β, LYN, and NAMPT might serve as biomarkers and therapeutic targets for IDD in the future.

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Section: Introductionmentioning

confidence: 99%

Development of a Novel Inflammatory-Associated Gene Signature and Immune Infiltration Patterns in Intervertebral Disc Degeneration

Lan

Guo

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Therefore, it is considered that infiltration by various cells, such as vascular endothelial cells, lymphocytes and macrophages occurs during the course of degeneration [3]. Cells in the intervertebral disc actively start to metabolize in response to mechanical and biochemical stimulations of the intervertebral disc via the matrix [4][5][6][7][8]. Furthermore, it is also considered that cells in the intervertebral disc become activated by themselves, thus causing tissue destruction in the intervertebral disc [9].…”

Section: Introductionmentioning

confidence: 99%

Kinetics of Tissue and Serum Matrix Metalloproteinase-3 and Tissue Inhibitor of Metalloproteinases-1 in Intervertebral Disc Degeneration and Disc Herniation.

Nishida

1999

Kurume Med. J.

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We have evaluated the correlation between disc herniation or degeneration and the levels of matrix metalloproteinase-3 (MMP-3) or tissue inhibitor of metalloproteinases-1 (TIMP-1). The lumbar discs obtained from 22 autopsied cadavers and 21 patients with lumbar disc herniation were examined. Immunohistochemical study: The number of MMP-3-producing and TIMP-1producing cells increased as disc herniation or degeneration progressed. Zymography: Activated type MMP-3 was observed in the normal and herniated intervertebral disc excluding the intervertebral disc with protrusion-type herniation. RT-PCR: The MMP-3 gene was expressed in all groups. However, the expression of the TIMP-1 gene was weak in the normal group as well as in the protrusion type disc herniation. Determination of tissue and serum levels of MMP-3 and TIMP-1 was increased as disc degeneration or herniation progressed. There were positive correlations between the number of MMP-3-producing or TIMP-1-producing cells in the intervertebral disc and the tissue or serum levels of MMP-3 and TIMP-1. These results suggested that MMP-3 and TIMP-1 were closely related to the progression of disc degeneration or herniation. The results also suggested that MMP-3 and TIMP-1 exhibited similar kinetics. Moreover, the serum levels of MMP-3 and TIMP-1 reflected the progression of disc degeneration and herniation.

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“…Therefore, we hypothesize that inflammation may be the key difference between symptomatic and asymptomatic IVD degeneration. 26 Since Naylar et al 27 proposed the autoimmunity of IVDs in 1975, meaning that cells in IVDs will be recognized by the immune system as foreign antigens and elicit immune reactions, in the past few decades, studies about the relationship between autoimmunity and disc degeneration and LBP have received growing attention. A number of studies have focused on the role of molecular immunology and the immune-related inflammatory response in LBP.…”

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confidence: 99%

The involvement of immune system in intervertebral disc herniation and degeneration

Lyu

Wang

et al. 2022

JOR Spine

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Intervertebral disc (IVD) herniation and degeneration contributes significantly to low back pain (LBP), of which the molecular pathogenesis is not fully understood. Disc herniation may cause LBP and radicular pain, but not all LBP patients have disc herniation. Degenerated discs could be the source of pain, but not all degenerated discs are symptomatic. We previously found that disc degeneration and herniation accompanied by inflammation. We further found that anti-inflammatory molecules blocked immune responses, alleviated IVD degeneration and pain. Based on our recent findings and the work of others, we hypothesize that immune system may play a prominent role in the production of disc herniation or disc degeneration associated pain. While the nucleus pulposus (NP) is an immune-privileged organ, the damage of the physical barrier between NP and systemic circulation, or the innervation and vascularization of the degenerated NP, on one hand exposes NP as a foreign antigen to immune system, and on the other hand presents compression on the nerve root or dorsal root ganglion (DRG), which both elicit immune responses induced by immune cells and their mediators. The inflammation can remain for a long time at remote distance, with various types of cytokines and immune cells involved in this pain-inducing process. In this review, we aim to revisit the autoimmunity of the NP, immune cell infiltration after break of physical barrier, the inflammatory activities in the DRG and the generation of pain. We also summarize the involvement of immune system, including immune cells and cytokines, in degenerated or herniated IVDs and affected DRG.

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Enzymic and Immunological Activity in the Intervertebral Disc

Cited by 55 publications

References 4 publications

Development of a Novel Inflammatory-Associated Gene Signature and Immune Infiltration Patterns in Intervertebral Disc Degeneration

Development of a Novel Inflammatory-Associated Gene Signature and Immune Infiltration Patterns in Intervertebral Disc Degeneration

Kinetics of Tissue and Serum Matrix Metalloproteinase-3 and Tissue Inhibitor of Metalloproteinases-1 in Intervertebral Disc Degeneration and Disc Herniation.

The involvement of immune system in intervertebral disc herniation and degeneration

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