Cellular senescence – Molecular mechanisms of intervertebral disc degeneration from an immune perspective

Song, Chao; Zhou, Yan; Cheng, Kang; Liu, Fei; Cai, Weiye; Zhou, Daqian; Chen, Rui; Shi, Houyin; Fu, Zhijiang; Chen, Jingwen; Liu, Zongchao

doi:10.1016/j.biopha.2023.114711

Cited by 27 publications

(30 citation statements)

References 70 publications

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“…Through bioinformatic data analysis, we clarified that senescence and apoptosis signaling pathways play an important role in the development of IVDD, and based on our group's previous research and literature, we believe that NPCs are important cells in IVDD. 3,14,30,31 Therefore, we hypothesize that SP1, CASP3, VEGFA, and IL- S7; Figure 9B). We can see from the WB results that CASP3 is different in the model and control groups in protein levels, but the statistical significance is less significant.…”

Section: Results Of Hub Gene Validationmentioning

confidence: 95%

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Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

Song,

Zhou,

Cheng

et al. 2023

JOR Spine

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BackgroundIntervertebral disc degeneration (IVDD) is a common chronic disease in orthopedics, and its molecular mechanisms are still not well explained.AimThis study's objective was to bioinformatics‐based discovery of IVDD biomarkers and immune‐inflammatory infiltrates.Materials and MethodsThe IVDD illness gene collection was gathered from GeneCards, DisGeNet, and gene expression profiles were chosen from the extensive Gene Expression Omnibus database (GSE124272, GSE150408, and GSE153761). The STRING database was used to create a network of protein–protein interactions, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases were used for functional enrichment analysis. Using hub genes, the immune cell infiltration between IVDD patient samples and control tissues was examined. Finally, quantitative polymerase chain reaction and Western blot experiments were used to verify the expression of hub genes.ResultsA total of 27 differentially expressed hub genes were identified by bioinformatics. According to GO and KEGG analyses, hub genes were prominent in immunological responses, chemokine‐mediated signaling pathways, and inflammatory responses, with the key signaling pathways engaged in cellular senescence, apoptosis, Th1 and Th2 cell differentiation, and Th17 cell differentiation. Immune cell infiltration research revealed that T cells, lymphocytes, B cells, and NK cells were decreased in IVDD patients while monocytes, neutrophils, and CD8 T cells were increased. The expression levels of the senescence hub genes SP1, VEGFA, IL‐6, and the apoptosis key gene CASP3 were considerably greater in the IVDD model group than in the control group, according to in vitro validation.ConclusionIn conclusion, the cellular senescence signaling pathway, the apoptosis signaling pathway, and associated hub genes play significant roles in the development and progression of IVDD, this finding may help direct future research on the senescence signaling route in IVDD.

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Section: Results Of Hub Gene Validationmentioning

confidence: 95%

“…3,14 Specifically, CS may accelerate disease progression in IVDD by activating immune-inflammatory responses through ROS, promoting intervertebral disc ECM breakdown, and apoptosis, as well as by inducing oxidative stress and autophagy. 14 Unfortunately, however, the specific role of aging and immunoinflammatory pathways in IVDD…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

Song,

Zhou,

Cheng

et al. 2023

JOR Spine

Self Cite

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“…The inflammatory response in disc degeneration exacerbates the progression of degenerative changes . The irregulated immune microenvironment during disc degeneration has been demonstrated by many studies . The levels of various proinflammatory factors, including IL-1, IL-6, and TNF-α, are significantly elevated in degenerative IVDs .…”

Section: Discussionmentioning

confidence: 99%

An Engineered Bionic Nanoparticle Sponge as a Cytokine Trap and Reactive Oxygen Species Scavenger to Relieve Disc Degeneration and Discogenic Pain

Yang,

Li,

Pan

et al. 2024

ACS Nano

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The progressive worsening of disc degeneration and related nonspecific back pain are prominent clinical issues that cause a tremendous economic burden. Activation of reactive oxygen species (ROS) related inflammation is a primary pathophysiologic change in degenerative disc lesions. This pathological state is associated with M1 macrophages, apoptosis of nucleus pulposus cells (NPC), and the ingrowth of pain-related sensory nerves. To address the pathological issues of disc degeneration and discogenic pain, we developed MnO 2 @TMNP, a nanomaterial that encapsulated MnO 2 nanoparticles with a TrkA-overexpressed macrophage cell membrane (TMNP). Consequently, this engineered nanomaterial showed high efficiency in binding various inflammatory factors and nerve growth factors, which inhibited inflammation-induced NPC apoptosis, matrix degradation, and nerve ingrowth. Furthermore, the macrophage cell membrane provided specific targeting to macrophages for the delivery of MnO 2 nanoparticles. MnO 2 nanoparticles in macrophages effectively scavenged intracellular ROS and prevented M1 polarization. Supportively, we found that MnO 2 @TMNP prevented disc inflammation and promoted matrix regeneration, leading to downregulated disc degenerative grades in the rat injured disc model. Both mechanical and thermal hyperalgesia were alleviated by MnO 2 @TMNP, which was attributed to the reduced calcitonin gene-related peptide (CGRP) and substance P expression in the dorsal root ganglion and the downregulated Glial Fibrillary Acidic Protein (GFAP) and Fos Proto-Oncogene (c-FOS) signaling in the spinal cord. We confirmed that the MnO 2 @TMNP nanomaterial alleviated the inflammatory immune microenvironment of intervertebral discs and the progression of disc degeneration, resulting in relieved discogenic pain.

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“…The main pathological feature of IDD is the loss of NPCs (Song et al, 2023). In the physiological environment where IVD is located, many stresses are present, including nutritional deficiency, mechanical load, inflammation, and oxidative stress (Johnson et al, 2015;Ma et al, 2013), which accelerate IDD by accelerating NPC senescence and apoptosis.…”

Section: Cell Ell B Biology Iology I International Nternationalmentioning

confidence: 99%

“…The main feature of IDD is the imbalance between anabolism and catabolism in IVD, resulting in the loss of nucleus pulposus cells (NPC), the degradation of extracellular matrix (ECM), and the eventual loss of the function and structural of IVD (Song et al, 2023).…”

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confidence: 99%

M6A methylation‐regulated autophagy may be a new therapeutic target for intervertebral disc degeneration

Tao,

Yu,

et al. 2024

Cell Biology International

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Degeneration of intervertebral discs is considered one of the most important causes of low back pain and disability. The intervertebral disc (IVD) is characterized by its susceptibility to various stressors that accelerate the senescence and apoptosis of nucleus pulposus cells, resulting in the loss of these cells and dysfunction of the intervertebral disc. Therefore, how to reduce the loss of nucleus pulposus cells under stress environment is the main problem in treating intervertebral disc degeneration. Autophagy is a kind of programmed cell death, which can provide energy by recycling substances in cells. It is considered to be an effective method to reduce the senescence and apoptosis of nucleus pulposus cells under stress. However, further research is needed on the mechanisms by which autophagy of nucleus pulposus cells is regulated under stress environments. M6A methylation, as the most extensive RNA modification in eukaryotic cells, participates in various cellular biological functions and is believed to be related to the regulation of autophagy under stress environments, may play a significant role in nucleus pulposus responding to stress. This article first summarizes the effects of various stressors on the death and autophagy of nucleus pulposus cells. Then, it summarizes the regulatory mechanism of m6A methylation on autophagy‐related genes under stress and the role of these autophagy genes in nucleus pulposus cells. Finally, it proposes that the methylation modification of autophagy‐related genes regulated by m6A may become a new treatment approach for intervertebral disc degeneration, providing new insights and ideas for the clinical treatment of intervertebral disc degeneration.

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Cellular senescence – Molecular mechanisms of intervertebral disc degeneration from an immune perspective

Cited by 27 publications

References 70 publications

Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

Bioinformatics‐based discovery of intervertebral disc degeneration biomarkers and immune‐inflammatory infiltrates

An Engineered Bionic Nanoparticle Sponge as a Cytokine Trap and Reactive Oxygen Species Scavenger to Relieve Disc Degeneration and Discogenic Pain

M6A methylation‐regulated autophagy may be a new therapeutic target for intervertebral disc degeneration

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