scholarly journals Elevated interleukin-6 expression levels are associated with intervertebral disc degeneration

2016 ◽  
Vol 11 (4) ◽  
pp. 1425-1432 ◽  
Author(s):  
XIAO DENG ◽  
FENG ZHAO ◽  
BAOLIN KANG ◽  
XIN ZHANG
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Interleukin 6 ◽  
Intervertebral Disc Degeneration ◽  
Expression Levels

scholarly journals Transcriptomics Study to Determine the Molecular Mechanism by which sIL-13Rα2-Fc Inhibits Caudal Intervertebral Disc Degeneration in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xin Wang ◽  
Jianshi Tan ◽  
Junhao Sun ◽  
Pengzhong Fang ◽  
Jinlei Chen ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Type I Collagen ◽  
Type Ii Collagen ◽  
Type I ◽  
Model Group ◽  
Expression Levels ◽  
Protein Levels ◽  
Collagen Protein

Background. Intervertebral disc degeneration is related to tissue fibrosis. ADAMTS can degrade the important components of the ECM during the process of intervertebral disc degeneration, ultimately resulting in the loss of intervertebral disc function. sIL-13Rα2-Fc can inhibit fibrosis and slow down the degeneration process, but the mechanism involved remains unclear. Objective. To determine the mechanism by which sIL-13Rα2-Fc inhibits ECM degradation and reduces intervertebral disc tissue fibrosis using a transcriptomics analysis. Methods. A rat model of caudal intervertebral disc degeneration was established, and Sirius red staining was used to observe the pathological changes in the caudal intervertebral disc. Transcriptome sequencing was employed to assess the gene expression profiles of the intervertebral disc tissues in the model group and the sIL-13Rα2-Fc-treated group. Differentially expressed genes were identified and analyzed using GO annotation and KEGG pathway analyses. Real-time fluorescence quantitative PCR was used to verify the expression levels of candidate genes. The levels of GAG and HA were quantitatively assessed by ELISA, and the levels of collagen I and collagen II were analyzed by western blotting. Results. Sirius red staining showed that in the model group, the annulus fibrosus was disordered, the number of breaks increased, and the type I collagen protein levels increased, whereas in the sIL-13Rα2-Fc group, the annulus fibrosus was ordered, the number of breaks decreased, and the type II collagen protein levels increased. In comparison with the model group, we identified 58 differentially expressed genes in the sIL-13Rα2-Fc group, and these were involved in 35 signaling pathways. Compared with those in the model group, the mRNA expression levels of Rnux1, Sod2, and Tnfaip6 in the IL-13Rα2-Fc group were upregulated, and the mRNA expression levels of Aldh3a1, Galnt3, Fgf1, Celsr1, and Adamts8 were downregulated; these results were verified by real-time fluorescence quantitative PCR. TIMP-1 (an ADAMTS inhibitor) and TIMP-1 combined with the sIL-13Rα2-Fc intervention increased the levels of GAG and HA, inhibited the expression of type I collagen, and promoted the expression of type II collagen. Conclusion. Adamts8 may participate in the degradation of ECM components such as GAG and HA and lead to an imbalance in the ECM of the intervertebral disc, resulting in intervertebral disc degeneration. sIL-13Rα2-Fc promoted anabolism of the ECM and increased the levels of ECM components by inhibiting the expression of Adamts8, thus maintaining the dynamic equilibrium of the ECM and ultimately delaying intervertebral disc degeneration.

scholarly journals miR-142-3p and HMGB1 Are Negatively Regulated in Proliferation, Apoptosis, Migration and Autophagy of Cartilage Endplate Cells

2021 ◽  
Author(s):  
Bo Wang ◽  
Demin Ji ◽  
Wenhua Xing ◽  
Feng Li ◽  
Zhi Huang ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Vital Role ◽  
Luciferase Assay ◽  
Expression Levels ◽  
Cartilage Endplate

Abstract Background: cartilage endplate (CEP) degeneration plays a vital role in the pathological process of intervertebral disc degeneration. It has been previously reported that microRNAs may participate in the occurrence and development of intervertebral disc degeneration through regulating its’ target genes directly. The regulatory roles of miR-142-3p /HMGB1 in some orthopedic diseases have been determined successively, but there was no report about the degeneration of CEP. Therefore, we aimed to determine the regulation of miR-142-3p /HMGB1or potential molecular mechanisms on proliferation, apoptosis, migration, and autophagy of CEP cells.Methods: the target gene of miR-142-3p was determined by double luciferase assay. We selected ATDC5 cell lines. CCK-8 method was used to detect cell proliferation. Real-time fluorescence quantitative PCR was used to determine gene expression levels, and western blot analysis was used to determine protein expression levels. We chose the flow cytometry to measure cell apoptosis and cell cycle.Results: the result of luciferase detection showed that the target gene of miR-142-3p in CEP cells was HMGB1. Knockdown the miR-142-3p inhibited the expression level of HMGB1, the proliferation and migration of CEP cells, but it promoted apoptosis of CEP cells. In addition, the detection results of the proteins related to apoptosis or autophagy showed that knockdown of miR-142-3p promoted apoptosis and autophagy.Conclusion: The negative regulation of miR-142-3p /HMGB1 can affect the proliferation, apoptosis, migration, and autophagy of CEP cells. Our results provided a new idea for the targeted treatment of CEP degeneration by inhibiting the expression of HMGB1.

scholarly journals Oxymatrine suppresses IL-1β-induced degradation of the nucleus pulposus cell and extracellular matrix through the TLR4/NF-κB signaling pathway

2020 ◽  
Vol 245 (6) ◽  
pp. 532-541
Author(s):  
Kang Wei ◽  
Jun Dai ◽  
Zhenggang Wang ◽  
Yaping Pei ◽  
Yan Chen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Interleukin 6 ◽  
Intervertebral Disc Degeneration ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Matrix Degradation ◽  
Nucleus Pulposus Cells

Intervertebral disc degeneration is the main cause of low back pain. However, its pathomechanism has not been fully clarified yet. Previous studies have indicated that inflammation may lead to apoptosis of nucleus pulposus cells and break the balance between anabolism and catabolism of the nucleus pulposus extracellular matrix. The purpose of this study is to explore the mitigative effect of oxymatrine on extracellular matrix degradation and apoptosis of nucleus pulposus cells after interleukin-1 beta-induced inflammation, and its possible signaling pathway. We examined the gene and protein levels of collagen II, aggrecan, and MMPs (MMP2/3/9/13) and interleukin 6 in nucleus pulposus cells. The results demonstrated that oxymatrine could reduce extracellular matrix degradation and apoptosis of nucleus pulposus cells; interleukin-1 beta prompted the expression of MMPs and interleukin 6 through TLR4/NF-κB axis, while oxymatrine reduced the expression of MMPs and TNF-α induced by interleukin-1 beta. Moreover, TAK 242, as a small molecule inhibitor of TLR4 signaling, was used to detect the effect of oxymatrine on the TLR4/NF-κB signaling. The final experimental results show that oxymatrine could reduce the inflammatory response of nucleus pulposus cells and degradation of nucleus pulposus tissue. Oxymatrine may be a potential medicine to reduce disc inflammation and relieve intervertebral disc degeneration by inhibiting the TLR4/NF-κB signal pathway. Impact statement Currently, drug therapy is a potential treatment for patients with intervertebral disc degeneration. In the present research, oxymatrine intervenes in intervertebral disc degeneration effectively via regulating inflammation in intervertebral disc degeneration rats. Our research highlights the therapeutic potential of oxymatrine in the treatment of intervertebral disc degeneration.

scholarly journals Hub Genes and Key Pathways of Intervertebral Disc Degeneration: Bioinformatics Analysis and Validation

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhiwen Zhang ◽  
Qiong Wang ◽  
Yang Li ◽  
Bangzhi Li ◽  
Liming Zheng ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Mrna Expression ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Bioinformatics Analysis ◽  
Mrna Levels ◽  
Hub Genes ◽  
Expression Levels ◽  
Ppi Networks ◽  
Mrna Expression Levels

Objective. To identify significant pathways and genes in intervertebral disc degeneration (IDD) based on bioinformatics analysis. Design. The GEO database was used to download the GSE124272 dataset. Differentially expressed genes (DEGs) were analyzed using Limma package in R language. Then, gene ontologies (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) networks were used to further identify hub genes. The mRNA expression levels of top six hub genes were verified. Results. We found 563 DEGs, of which 214 were upregulated and 349 were downregulated. The top 5 GO terms and pathways were shown including immune response, cell cycle, and p53 pathway. Based on the PPI analysis, we verified the mRNA expression levels of 6 hub genes. The mRNA levels of CHEK1, CDCA2, SKA3, and KIF20A were upregulated in degenerative NP tissue than in healthy NP tissue. However, the mRNA level of BUB1 and SPC25 was downregulated. Conclusions. This study may provide new biomarkers for the IDD and treatments to repair IDD related to CHEK1, CDCA2, SKA3, BUB1, KIF20A, and SPC25.

scholarly journals Knockout of miR-17-92 Cluster Protect Against Intervertebral Disc Degeneration by Inhibiting Apoptosis of Nucleus Pulposus Cells in Mice via the Activation of PI3K/Akt Pathway

2021 ◽  
Author(s):  
Yingjun Guo ◽  
Yang Meng ◽  
Hao Liu ◽  
Xiaofei Wang ◽  
Ying Hong ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Mrna Level ◽  
Akt Pathway ◽  
Functional Genes ◽  
Control Group ◽  
Expression Levels ◽  
Protein Levels

Abstract Background: microRNA(miR)-17-92 cluster is involved in a variety of physiological and pathological processes, and the purpose of this study is to preliminarily explore the role of miR-17-92 cluster in disc degeneration and the corresponding mechanisms.Methods: Hematoxylin and Eosin (HE) and Safranin O Staining were used to evaluate the degeneration of intervertebral disc. qRT-PCR was applied to evaluate the mRNA level of miR-17-92 cluster and functional genes of nucleus pulposus (NP) tissues, whose protein level was evaluated with Western-blot. Terminal-Deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) was used to evaluate the apoptotic level of nucleus pulposus cell (NPC).Results: The expression levels of members of the miR-17-92 cluster were significantly increased in the NP tissues from patients with intervertebral disc degeneration (IVDD). Furthermore, in the 3-months and 24-months miR-17-92-ccKO mice, the degree of IVDD was significantly lower than that of the control group. At the same time, we also detected the expression levels of related functional genes in the NP tissues of mice in two groups. The results showed that the mRNA and protein levels of Bax and Caspase-3 in the knockout group were significantly lower than those in the control group, and the mRNA and protein levels of Bcl-2 were significantly higher. The TUNEL results showed that the apoptosis level of NPCs in the 3-month knockout mice was significantly lower than that in the control group. Finally, the assessment of pathway-related protein levels showed that p-Ser473-Akt expression ratio in the nucleus pulposus of mice in the knockout group were significantly increased, suggesting that the PI3K/Akt pathway was activated after miR-17-92 cluster knockout.Conclusion: To sum up, miR-17-92 cluster does play an important regulating role in IVDD, and the results showed that miR-17-92 cluster could inhibiting NPCs apoptosis by activating PI3K/Akt pathway, eventually producing protective effect against IVDD.

scholarly journals p16 deficiency attenuates intervertebral disc degeneration by adjusting oxidative stress and nucleus pulposus cell cycle

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Hui Che ◽  
Jie Li ◽  
You Li ◽  
Cheng Ma ◽  
Huan Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Matrix Protein ◽  
Nucleus Pulposus Cell ◽  
Lumbar Intervertebral Disc ◽  
Expression Levels ◽  
Intervertebral Disc Height

The cell cycle regulator p16 is known as a biomarker and an effector of aging. However, its function in intervertebral disc degeneration (IVDD) is unclear. In this study, p16 expression levels were found to be positively correlated with the severity of human IVDD. In a mouse tail suspension (TS)-induced IVDD model, lumbar intervertebral disc height index and matrix protein expression levels were reduced significantly were largely rescued by p16 deletion. In TS mouse discs, reactive oxygen species levels, proportions of senescent cells, and the senescence-associated secretory phenotype (SASP) were all increased, cell cycling was delayed, and expression was downregulated for Sirt1, superoxide dismutase 1/2, cyclin-dependent kinases 4/6, phosphorylated retinoblastoma protein, and transcription factor E2F1/2. However, these effects were rescued by p16 deletion. Our results demonstrate that p16 plays an important role in IVDD pathogenesis and that its deletion attenuates IVDD by promoting cell cycle and inhibiting SASP, cell senescence, and oxidative stress.

scholarly journals miR-142-3p and HMGB1 Are Negatively Regulated in Proliferation, Apoptosis, Migration, and Autophagy of Cartilage Endplate Cells

Cartilage ◽  
2021 ◽  
pp. 194760352110124
Author(s):  
Bo Wang ◽  
Demin Ji ◽  
Wenhua Xing ◽  
Feng Li ◽  
Zhi Huang ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Assay ◽  
Expression Levels ◽  
Cartilage Endplate

Background Cartilage endplate (CEP) degeneration plays a vital role in the pathological process of intervertebral disc degeneration. It has been previously reported that microRNAs may participate in the occurrence and development of intervertebral disc degeneration through regulating its target genes directly. The regulatory roles of miR-142-3p/HMGB1 in some orthopedic diseases have been determined successively, but there was no report about the degeneration of CEP. Therefore, we aimed to determine the regulation of miR-142-3p/HMGB1 or potential molecular mechanisms on proliferation, apoptosis, migration, and autophagy of CEP cells. Methods The target gene of miR-142-3p was determined by double luciferase assay. We selected ATDC5 cell lines. CCK-8 method was used to detect cell proliferation. Real-time fluorescence quantitative polymerase chain reaction was used to determine gene expression levels, and western blot analysis was used to determine protein expression levels. We chose flow cytometry to measure cell apoptosis and cell cycle. Results The result of luciferase detection showed that the target gene of miR-142-3p in CEP cells was HMGB1. Knockdown of the miR-142-3p inhibited the expression level of HMGB1, the proliferation and migration of CEP cells, but it promoted apoptosis of CEP cells. In addition, the detection results of the proteins related to apoptosis or autophagy showed that knockdown of miR-142-3p promoted apoptosis and autophagy. Conclusion The negative regulation of miR-142-3p/HMGB1 can affect the proliferation, apoptosis, migration, and autophagy of CEP cells. Our results provide a new idea for the targeted treatment of CEP degeneration by inhibiting the expression of HMGB1.

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