A novel mechanism of intervertebral disc degeneration: imbalance between autophagy and apoptosis

Epigenomics ◽  
2020 ◽  
Vol 12 (13) ◽  
pp. 1095-1108
Author(s):  
Guoyong Xu ◽  
Chong Liu ◽  
Jie Jiang ◽  
Tuo Liang ◽  
Chaojie Yu ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Expression Profiles ◽  
Circular Rna ◽  
Molecular Structures ◽  
Circular Rnas ◽  
Nucleus Pulposus Cells ◽  
Competitive Endogenous Rna

Aim: To identify a key competitive endogenous RNA network for intervertebral disc degeneration. Materials & methods: Based on circular RNA, microRNA and mRNA expression profiles of nucleus pulposus cells, a variety of bioinformatics methods were used to screen key molecular structures and construct competitive endogenous RNA networks. Results: 190 upregulated genes and 77 downregulated genes were identified. Gene ontology/Kyoto Encyclopedia of Genes and Genomes functional analysis showed that autophagy was out of balance with apoptosis. Nine hub genes, five hub microRNAs and eight hub circular RNAs were obtained through progressive reverse prediction and verification. Conclusion: We believe that disc degeneration is caused by an imbalance between autophagy and apoptosis in nucleus pulposus cells, which may provide nonsurgical treatment for the future delay or prevention of spinal degenerative diseases associated with intervertebral disc degeneration.

scholarly journals Silencing NDC80, RAD21 and BUB1B ameliorates intervertebral disc degeneration by promoting proliferation and inhibiting apoptosis of nucleus pulposus cells

2020 ◽  
Author(s):  
Bin Zhang ◽  
Yueyan Guan ◽  
Weixiao Liu ◽  
Wei Guo ◽  
Peng Peng ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Expression Profiles ◽  
Nucleus Pulposus Cells ◽  
Pathogenic Genes ◽  
Genes Expression ◽  
Underlying Mechanisms ◽  
Microarray Datasets

Abstract Background Intervertebral disc degeneration (IVDD) is a commonly occurring musculoskeletal disorder, which is closely associated with low back pain. Accumulating evidence has demonstrated that dysregulated genes expression profiles play important roles in pathogenesis of IVDD. Hence, the current study was aimed to identify key genes to understand underlying mechanisms and therapeutic targets of IVDD. Methods Microarray datasets of GSE34095, GSE63492 and GSE45856 were downloaded to identify the hub genes that participate in the IVDD pathogenesis. After establishment of rat IVDD models, the expressions of NDC80, BUB1B and RAD21 in rat IVDD samples were evaluated by reverse transcription quantitative PCR (RT-qPCR) and immunochemistry. Subsequently, we assessed the proliferation, cycle and apoptosis of nucleus pulposus (NP) cells that transfected with siRNA-NDC80, siRNA-BUB1B and siRNA-RAD21. Results Our results showed indicated that NDC80, BUB1B and RAD21 were the key pathogenic genes with higher expression in IVDD rats, and silencing of NDC80, BUB1B and RAD21 gene could promote the aggrecan and collagen II synthesis, cell cycle and proliferation of NP cells, and inhibit NP cells apoptosis. Conclusion Our study suggests that silencing NDC80, RAD21 and BUB1B genes ameliorates intervertebral disc degeneration by promoting proliferation and inhibiting apoptosis of nucleus pulposus cells.

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.

Profiling and bioinformatics analysis of differentially expressed circular RNAs in human intervertebral disc degeneration

2019 ◽  
Vol 51 (6) ◽  
pp. 571-579 ◽  
Author(s):  
Shunmin Wang ◽  
Jingchuan Sun ◽  
Haisong Yang ◽  
Weiguo Zou ◽  
Bing Zheng ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Functional Changes ◽  
Qrt Pcr ◽  
Reverse Transcription Pcr ◽  
Microarray Expression

AbstractThe functional changes of nucleus pulposus (NP) cells are considered to be the initiating factors of intervertebral disc degeneration (IDD), and the differentially expressed circRNAs in NP cells may play an important role in the process of IDD. To identify circular RNAs (circRNAs) associated with human IDD, we isolated the NP cells from human degenerated and non-degenerated intervertebral disc and identified NP cells by microscopy and cell proliferation. CircRNA microarray expression profiles were obtained from NP cells of degenerated and non-degenerated intervertebral disc and further validated by quantitative reverse transcription PCR (qRT-PCR). The expression data were analyzed by bioinformatics. Microarray analysis identified 7294 circRNAs differentially expressed in degenerated human IDD NP cells. Among them, 3724 circRNAs were up-regulated and 3570 circRNAs were down-regulated by more than 2 folds. After validating by qRT-PCR, we predicted the possible miRNAs of the top dysregulated circRNAs using TargetScan, and miRanda. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most modulated circRNAs regulate the viability, degradation, apoptosis and oxidative stress in NP cells, and the possible mechanism underlying IDD was discussed. These results revealed that circRNAs may play a role in IDD and might be a promising candidate molecular target for gene therapy.

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