Sesamin inhibits lipopolysaccharide-induced inflammation and extracellular matrix catabolism in rat intervertebral disc

Li, Kang; Li, Yan; Xu, Bo; Mao, Lu; Zhao, Jie

doi:10.1080/03008207.2016.1182998

Cited by 29 publications

(21 citation statements)

References 59 publications

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“…Interestingly, the top 5 enrichments of GO BP included response to lipopolysaccharide (GO BP:003249), negative regulation of cell proliferation (GO BP:0008285), and response to hypoxia (GO BP:0001666). Lots of literatures reported that lipopolysaccharide could induce inflammatory response of IVD; thus, the biological processes in response to lipopolysaccharide indicated an important role of inflammation in NPC senescence [43]. Besides, hypoxia and inflammation are two important characteristics of the environment of degenerated IVD [44]; thus, these results highlighted a vital role of a local environment in NPC senescence.…”

Section: Discussionmentioning

confidence: 99%

Identification of Aberrantly Expressed Genes during Aging in Rat Nucleus Pulposus Cells

Cheng

Lin

et al. 2019

Stem Cells International

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Nucleus pulposus cells (NPCs) play a vital role in maintaining the homeostasis of the intervertebral disc (IVD). Previous studies have discovered that NPCs exhibited malfunction due to cellular senescence during disc aging and degeneration; this might be one of the key factors of IVD degeneration. Thus, we conducted this study in order to investigate the altered biofunction and the underlying genes and pathways of senescent NPCs. We isolated and identified NPCs from the tail discs of young (2 months) and old (24 months) SD rats and confirmed the senescent phenotype through SA-β-gal staining. CCK-8 assay, transwell assay, and cell scratch assay were adopted to detect the proliferous and migratory ability of two groups. Then, a rat Gene Chip Clariom™ S array was used to detect differentially expressed genes (DEGs). After rigorous bioinformatics analysis of the raw data, totally, 1038 differentially expressed genes with a fold change>1.5 were identified out of 23189 probes. Among them, 617 were upregulated and 421 were downregulated. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted and revealed numerous number of enriched GO terms and signaling pathways associated with senescence of NPCs. A protein-protein interaction (PPI) network of the DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. Module analysis was conducted for the PPI network using the MCODE plugin in Cytoscape. Hub genes were identified by the CytoHubba plugin in Cytoscape. Derived 5 hub genes and most significantly up- or downregulated genes were further verified by real-time PCR. The present study investigated underlying mechanisms in the senescence of NPCs on a genome-wide scale. The illumination of molecular mechanisms of NPCs senescence may assist the development of novel biological methods to treat degenerative disc diseases.

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Section: Discussionmentioning

confidence: 99%

Identification of Aberrantly Expressed Genes during Aging in Rat Nucleus Pulposus Cells

Cheng

Lin

et al. 2019

Stem Cells International

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“…The ECM produced by NP cells performs a vital role in the maintenance of disc physiology, and ECM degradation is a major feature of IVDD 38 . MMPs and ADAMTS are catabolic enzymes that degrade the ECM in IVDD 39 . Our data indicated that BBR could effectively inhibit ECM degradation.…”

Section: Discussionmentioning

confidence: 99%

Berberine suppresses apoptosis and extracellular matrix (ECM) degradation in nucleus pulposus cells and ameliorates disc degeneration in a rodent model

et al. 2018

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Intervertebral disc degeneration (IVDD) is a chronic disease with complicated pathology involving nucleus pulposus (NP) cell apoptosis and extracellular matrix (ECM) degradation. Previous studies have shown that moderate autophagy has a protective effect against apoptosis in NP cells. Berberine (BBR) is an alkaloid compound with many beneficial properties including antimicrobial, anti-inflammatory, antioxidative, and anti-apoptotic activity. Recently, it was found to induce autophagy in various tissues as well. Thus, we hypothesized that BBR may exert a therapeutic effect on IVDD through autophagy activation. In this study, we investigated the effects of BBR on IVDD and delineated a potential mechanism. BBR treatment in vitro inhibited the expression of pro-apoptotic proteins induced by tert-butyl hydroperoxide (TBHP), and increased the expression of anti-apoptotic Bcl-2. Furthermore, it prevented ECM degradation by inhibiting the production of matrix-degrading enzymes. Additionally, BBR treatment significantly activated autophagy in NP cells. However, autophagy inhibition markedly suppressed BBR's effects on NP cell apoptosis and ECM degeneration, indicating that autophagy activation with BBR treatment is protective against IVDD. In vivo, BBR treatment increased the expression of LC3 in disc cells and prevented the development of IVDD in a needle puncture-induced rat model. Thus, BBR stimulates autophagy as a protective mechanism against NP cell apoptosis and ECM degeneration, revealing its therapeutic potential in the treatment of IVDD.

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“…Since therapeutic approaches for IVDD remain limited, biological anti‐inflammatory approaches to IVD regeneration have gained increasing interest. In cases of refractory LBP due to IVDD, anti‐inflammatory and/or anti‐degenerative therapies such as cytokine inhibition may relieve pain and slow down the progression of the disease 22‐31 . Several studies indicated that cyclooxygenase‐2 (COX2) inhibitors can reduce the inflammatory response in different models 25‐27 .…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory intervertebral disc cell and organ culture models induced by tumor necrosis factor alpha

Pfannkuche

Lang

et al. 2020

JOR Spine

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Inflammation plays an important role in the pathogenesis of intervertebral disc (IVD) degeneration. The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) has shown markedly higher expression in degenerated human disc tissue compared with healthy controls. Anti-inflammatory treatment targeting TNF-α has shown to alleviate discogenic pain in patients with low back pain. Therefore, in vitro and ex vivo inflammatory models utilizing TNF-α provide relevant experimental conditions for drug development in disc degeneration research. The current method article addressed several specific questions related to the model establishment. (a) The effects of bovine and human recombinant TNF-α on bovine nucleus pulposus (NP) cells were compared. (b) The required dose for an inflammatory IVD organ culture model with intradiscal TNF-α injection was studied. (c) The effect of TNF-α blocking at different stages of inflammation was evaluated. Outcomes revealed that bovine and human recombinant TNF-α induced equivalent inflammatory effects in bovine NP cells. A bovine whole IVD inflammatory model was established by intradiscal injection of 100 ng TNF-α/ cm 3 disc volume, as indicated by increased nitric oxide, glycosaminoglycan, interleukin 6 (IL-6), and interleukin 8 (IL-8) release in culture media, and upregulation of MMP3, ADAMTS4, IL-8, IL-6, and cyclooxygenase (COX)-2 expression in NP tissue. However, results in human NP cells showed that the time point of anti-inflammatory treatment was crucial to achieve significant effects. Furthermore, anticatabolic therapy in conjunction with TNF-α inhibition would be required to slow down the pathologic cascade of disc degeneration.

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Sesamin inhibits lipopolysaccharide-induced inflammation and extracellular matrix catabolism in rat intervertebral disc

Cited by 29 publications

References 59 publications

Identification of Aberrantly Expressed Genes during Aging in Rat Nucleus Pulposus Cells

Identification of Aberrantly Expressed Genes during Aging in Rat Nucleus Pulposus Cells

Berberine suppresses apoptosis and extracellular matrix (ECM) degradation in nucleus pulposus cells and ameliorates disc degeneration in a rodent model

Proinflammatory intervertebral disc cell and organ culture models induced by tumor necrosis factor alpha

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