scholarly journals Suramin attenuates intervertebral disc degeneration by inhibiting NF-κB signalling pathway

2021 ◽  
Vol 10 (8) ◽  
pp. 498-513
Author(s):  
Zi-Miao Liu ◽  
Cheng-Chang Lu ◽  
Po-Chih Shen ◽  
Shih-Hsiang Chou ◽  
Chia-Lung Shih ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Treatment Options ◽  
Underlying Mechanism ◽  
Mitogen Activated Protein Kinase ◽  
Blue Staining ◽  
Alcian Blue Staining

Aims Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Methods Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining. Results Suramin inhibited IL-1β-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1β-treated NP cells. IL-1β-induced inflammation, assessed by IL-1β, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1β-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments. Conclusion Suramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells. Cite this article: Bone Joint Res 2021;10(8):498–513.

scholarly journals Unravelling the role of Mesenchymal Stem/Stromal Cells Secretome in intervertebral disc degeneration in a pro-inflammatory/degenerative ex vivo model

2020 ◽  
Author(s):  
JR Ferreira ◽  
GQ Teixeira ◽  
E Neto ◽  
C Ribeiro-Machado ◽  
AM Silva ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Stromal Cells ◽  
Intervertebral Disc Degeneration ◽  
Ex Vivo ◽  
Ex Vivo Model

Abstract The authors have withdrawn this preprint due to author disagreement.

scholarly journals Ligustrazine Prevents Intervertebral Disc Degeneration via Suppression of Aberrant TGFβ Activation in Nucleus Pulposus Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Shufen Liu ◽  
Yuhao Cheng ◽  
Yuqi Tan ◽  
Jingcheng Dong ◽  
Qin Bian
Keyword(s):  
Growth Factor ◽  
Mouse Model ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Ex Vivo ◽  
Tissue Growth ◽  
Nucleus Pulposus Cells

Objectives. Aberrant transforming growth factor β (TGFβ) activation is detrimental to both nucleus pulposus (NP) cells and cartilage endplates (CEPs), which can lead to intervertebral disc degeneration (IDD). Ligustrazine (LIG) reduces the expression of inflammatory factors and TGFβ1 in hypertrophic CEP to prevent IDD. In this study, we investigate the effects of LIG on NP cells and the TGFβ signaling. Design. LIG was injected to the lumbar spinal instability (LSI) mouse model. The effect of LIG was evaluated by intervertebral disc (IVD) score in the LSI mouse model. The expression of activated TGFβ was examined using immunostaining with pSmad2/3 antibody. The upright posture (UP) rat model was also treated and evaluated in the same manner to assess the effect of LIG. In ex vivo study, IVDs from four-week old mice were isolated and treated with 10−5, 10−6, and 10−7 M of LIG. We used western blot to detect activated TGFβ expression. TGFβ-treated human nucleus pulposus cells (HNPCs) were cotreated with optimized dose of LIG in vitro. Immunofluorescence staining was performed to determine pSmad2/3, connective tissue growth factor (CCN2), and aggrecan (ACAN) expression levels. Results. IVD score and the percentage of pSmad2/3+ NP cells were low in LIG-treated LSI mice in comparison with LSI mice, but close to the levels in the Sham group. Similarly, LIG reduced the overexpression of TGFβ1 in NP cells. The inhibitory effect of LIG was dose dependent. A dose of 10−5 M LIG not only strongly attenuated Smad2/3 phosphorylation in TGFβ-treated IVD ex vivo but also suppressed pSmad2/3, CCN2, and ACAN expression in TGFβ-treated NP cells in vitro. Conclusions. LIG prevents IDD via suppression of TGFβ overactivation in NP cells.

Multiparametric MR Investigation of Proteoglycan Diffusivity, T 2 Relaxation, and Concentration in an Ex Vivo Model of Intervertebral Disc Degeneration

2019 ◽  
Vol 51 (5) ◽  
pp. 1390-1400 ◽  
Author(s):  
Min Wang ◽  
Adrian Tsang ◽  
Vivian Tam ◽  
Danny Chan ◽  
Peng Cao ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Ex Vivo ◽  
Ex Vivo Model

scholarly journals Mechanism of Long Noncoding RNA HOTAIR in Nucleus Pulposus Cell Autophagy and Apoptosis in Intervertebral Disc Degeneration

2022 ◽  
Vol 2022 ◽  
pp. 1-18
Author(s):  
Shujun Zhang ◽  
Sheng Song ◽  
Wei Cui ◽  
Xueguang Liu ◽  
Zhenzhong Sun
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Noncoding Rna ◽  
Intervertebral Disc Degeneration ◽  
Intervertebral Discs ◽  
Luciferase Reporter ◽  
Blue Staining ◽  
Tunel Staining ◽  
Lncrna Hotair

Objective. Intervertebral disc degeneration (IDD) contributes to cervical and lumbar diseases. Long noncoding RNAs (lncRNAs) are implicated in IDD. This study explored the mechanism of lncRNA HOTAIR in IDD. Methods. Normal and degenerative nucleus pulposus (NP) cells were isolated from NP tissues obtained in intervertebral disc surgery. Cell morphology was observed by immunocytochemistry staining and toluidine blue staining. NP cell markers were detected by RT-qPCR. Proliferation was detected by MTT assay. Autophagy-related proteins were detected by Western blot. Autophagosome was observed by monodansylcadaverine fluorescence staining. Apoptosis was detected by TUNEL staining and flow cytometry. si-HOTAIR and/or miR-148a inhibitor was introduced into degenerative NP cells. Binding relationships among HOTAIR, miR-148a, and PTEN were predicted and verified by dual-luciferase reporter assay and RNA pull-down. Finally, IDD rat models were established. Rat caudal intervertebral discs were assessed by HE staining. Expressions of HOTAIR, miR-148a, and PTEN were determined by RT-qPCR. Results. HOTAIR was highly expressed in degenerative NP cells p < 0.05 . si-HOTAIR inhibited degenerative NP cell apoptosis and autophagy p < 0.05 . HOTAIR upregulated PTEN as a sponge of miR-148a. miR-148a was poorly expressed in degenerative NP cells. miR-148a deficiency partially reversed the inhibition of si-HOTAIR on degenerative NP cell autophagy and apoptosis (all p < 0.05 ). In vivo assay confirmed that si-HOTAIR impeded autophagy and apoptosis in intervertebral disc tissues, thus improving pathological injury in IDD rats (all p < 0.05 ). Conclusion. LncRNA HOTAIR promoted NP cell autophagy and apoptosis via promoting PTEN expression as a ceRNA of miR-148a in IDD.

scholarly journals Integrated Analysis of a circRNA-miRNA-mRNA Axis in Intervertebral Disc Degeneration

2020 ◽  
Author(s):  
Laifu Wei ◽  
Bizhi Tu ◽  
Fei Gao ◽  
Jun Qian
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Underlying Mechanism ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Integrated Analysis ◽  
Control Group ◽  
Common Symptom ◽  
Sequencing Data

Abstract Background: Low back pain (LBP) is a common symptom in daily life and one of the primary causes is intervertebral disc degeneration (IDD). Growing studies have indicated that circular RNAs (circRNAs) are intimately associated with IDD; however, the underlying mechanism has not yet been elucidated. We aimed to explore how circRNAs regulate IDD in an effort to provide novel insight for clinical diagnosis and treatment. Methods: The sequencing data of circRNAs, microRNAs (miRNAs), and mRNA were acquired from Gene Expression Omnibus (GEO) datasets. By analyzing the dataset consisting of a control group and degenerated group, differentially expressed circRNAs, miRNAs, and mRNAs were collected, and then the intersection of circRNAs, miRNAs, and mRNAs was screened. According to these intersectional RNAs, we constructed an integrally circRNA-miRNA-mRNA network. Finally, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we further clarified functions of the intersectional mRNA in IDD. Results: we obtained 620 differentially expressed circRNAs(DEcircRNAs), 13 miRNA (DEmiRNA), 273 mRNAs(DEmRNAs), 12 intersectional miRNAs, and 47 intersectional mRNAs. Finally, based on interactional 8 circRNA, 5 miRNAs and 15 mRNAs, an integrally circRNA-miRNA-mRNA network was constructed. Eight circRNAs, contained hsa_circ_0032254, hsa_circ_0003183, hsa_circ_0032253, hsa_circ_0001293, hsa_circ_0004565, hsa_circ_0091570, hsa_circ_0077526, and hsa_circ_0057552, may regulate IDD onset and progression by acting as competing endogenous RNAs. The results of GO and KEGG analyses implied that the targeted genes might significantly correlate to IDD.Conclusion: our findings improved a better understanding of the circRNA-related ceRNA regulatory mechanism in IDD and offered possible targets for IDD treatment.

scholarly journals BIOMEDICAL ENGINEERING METHODS AS POTENTIAL TREATMENT OPTIONS FOR INTERVERTEBRAL DISC DEGENERATION

2005 ◽  
Vol 17 (02) ◽  
pp. 97-100
Author(s):  
SHU-HUA YANG ◽  
FENG-HUEI LIN
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Biomedical Engineering ◽  
Intervertebral Disc Degeneration ◽  
Clinical Symptoms ◽  
Treatment Options ◽  
Current Treatment ◽  
Potential Treatment ◽  
Spinal Disorders ◽  
Health Cost

Degeneration of the intervertebral disc (IVD) and associated spinal disorders are a leading cause of morbidity resulting in substantial pain and increased health cost. Current treatment options may relieve some clinical symptoms but will never stop further degeneration in the IVD. In recent years, several investigations have been carried out trying to regenerate IVD tissue. These biomedical engineering methods aim to retard or even reverse the degenerative process and possibly regain a healthy IVD. In this review, recent progresses on each category of biomedical engineering approaches will be briefly introduced.

scholarly journals Effects of Single Local Injection of Local Anesthetic Agents on Intervertebral Disc Degeneration: Ex Vivo and Long-Term in Vivo Experimental Study

2015 ◽  
Vol 5 (1_suppl) ◽  
pp. s-0035-1554227-s-0035-1554227
Author(s):  
Koji Iwasaki ◽  
Hideki Sudo ◽  
Katsuhisa Yamada ◽  
Norimasa Iwasaki
Keyword(s):  
Experimental Study ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Local Anesthetic ◽  
Intervertebral Disc Degeneration ◽  
Ex Vivo ◽  
Local Injection ◽  
Anesthetic Agents

scholarly journals Analysis of key genes and pathways associated with the pathogenesis of intervertebral disc degeneration

2020 ◽  
Author(s):  
Shiyu Hu ◽  
Yucheng Fu ◽  
Bin Yan ◽  
Zhe Shen ◽  
Tao Lan
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Target Genes ◽  
Underlying Mechanism ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Matrix Organization ◽  
Underlying Mechanisms ◽  
Upregulated Genes

Abstract Background: Intervertebral disc degeneration (IDD) is widely known as a main contributor to low back pain which has a negative socioeconomic impact worldwide. However, the underlying mechanism remains unclear. This study aims to analyze the dataset GSE23130 using bioinformatics methods to identify the pivotal genes and pathways associated with IDD.Material/Methods: The gene expression data of GSE23130 was downloaded and differentially expressed genes (DEGs) were extracted from 8 samples and 15 controls. GO and KEGG pathway enrichment analyses were performed. Also, Protein–protein interaction (PPI) network was constructed and visualized, followed by identification of hub genes and key module.Results: A total of 30 downregulated and 79 upregulated genes were identified. The DEGs mainly enriched in regulation of protein catabolic process, extracellular matrix organization, collagen fibril organization, and extracellular structure organization. Meanwhile, we found that most of DEGs were primarily enriched in PI3K-Akt signaling pathway. The top 10 hub genes were FN1, COL1A2, SPARC, COL3A1, CTGF, LUM, TIMP1, THBS2, COL5A2, and TGFB1.Conclusions: In summary, key candidate genes and pathway were identified by using integrated bioinformatics analysis, which may provide insights into underlying mechanisms and offer potential target genes for the treatment of IDD.

scholarly journals Analysis of key genes and pathways associated with pathogenesis of intervertebral disc degeneration

2020 ◽  
Author(s):  
Shiyu Hu ◽  
Yucheng Fu ◽  
Bin Yan ◽  
Zhe Shen ◽  
Tao Lan
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Target Genes ◽  
Underlying Mechanism ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Matrix Organization ◽  
Underlying Mechanisms ◽  
Upregulated Genes

Abstract Background: Intervertebral disc degeneration (IDD) is widely known as a main contributor to low back pain which has a negative socioeconomic impact worldwide. However, the underlying mechanism remains unclear. The aim of this study is to analyze the dataset GSE23130 using bioinformatics methods to identify the pivotal genes and pathways associated with IDD. Material/Methods: The gene expression data of GSE23130 was downloaded and differentially expressed genes (DEGs) were extracted from 8 samples and 15 controls. GO and KEGG pathway enrichment analyses were performed. In addition, Protein–protein interaction (PPI) network was constructed and visualized, followed by identification of hub genes and key module. Results: A total of 30 downregulated and 79 upregulated genes were identified. The DEGs mainly enriched in regulation of protein catabolic process, extracellular matrix organization, collagen fibril organization, and extracellular structure organization. Meanwhile, we found that most of DEGs were primarily enriched in PI3K-Akt signaling pathway. The top 10 hub genes were FN1, COL1A2, SPARC, COL3A1, CTGF, LUM, TIMP1, THBS2, COL5A2, and TGFB1. Conclusions: In summary, key candidate genes and pathway were identified by using integrated bioinformatics analysis, which may provide insights into underlying mechanisms and offer potential target genes for the treatment of IDD.

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