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.

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.

scholarly journals Efficacy of Platelet-Rich Plasma Containing Xenogenic Adipose Tissue-Derived Stromal Cells on Restoring Intervertebral Disc Degeneration: A Preclinical Study in a Rabbit Model

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Chao Ma ◽  
Ran Wang ◽  
Dingliang Zhao ◽  
Naikun Wang ◽  
Ying Han ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Stromal Cells ◽  
Signal Intensity ◽  
Intervertebral Disc Degeneration ◽  
Platelet Rich Plasma ◽  
Rabbit Model ◽  
Control Group ◽  
Arterial Blood

Objective. Platelet-rich plasma (PRP) containing multiple growth factors is a promising strategy for disc degeneration. Thus, this study hypothesizes that the combination of PRP and adipose tissue-derived stromal cells (ADSCs) may repair degenerative disc more effectively than using each one of them alone. Methods. The model of early intervertebral disc degeneration was induced by annular puncture in the New Zealand rabbit. Autologous PRP was extracted from fresh arterial blood by using two centrifugation techniques. ADSC was offered by the Center for Clinic Stem Cell Research. Four weeks after the first experiment, PRP or ADSCs or a combination of PRP and ADSCs was injected into the punctured intervertebral disc. Four weeks later, disc height and signal intensity on T2-weighted magnetic resonance imaging (MRI) were assessed. Results. One month after puncture, we detected relatively narrow discs and lower signal intensity in MRI T2-weighted images. At four weeks after injection, the PRP-ADSC group statistically significantly restored discs, compared with PRP, ADSCs, or negative control group. Conclusions. The combination of PRP and ADSCs shows an effective potential to restore degenerated intervertebral discs in the rabbit.

scholarly journals CircGLCE alleviates intervertebral disc degeneration by regulating apoptosis and matrix degradation through the targeting of miR-587/STAP1

2020 ◽  
Author(s):  
Zhonghui Chen ◽  
Weibing Zhang ◽  
Ming Deng ◽  
Yan Zhou ◽  
Yaming Li
Keyword(s):  
Flow Cytometry ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Western Blotting ◽  
Intervertebral Disc Degeneration ◽  
Luciferase Assay ◽  
Circular Rnas ◽  
Tunel Staining ◽  
Immunofluorescence Analysis

AbstractBackgroundIntervertebral disc degeneration (IDD) can induce profound global socioeconomic burdens. Recent studies have suggested that circular RNAs might have crucial functions in the progression of IDD. The purpose of this study was to identify a specific circular RNA and to investigate its regulatory mechanism in IDD.MethodsCircGLCE was selected after microarray analyses and was further analysed by RT-qPCR and FISH. After silencing CircGLCE, its function was assessed with RT-qPCR, immunofluorescence analysis and flow cytometry. Based on Sanger sequencing, miR-587 was identified as a direct target of CircGLCE, and it was further examined with RNA pulldown assays, RT-qPCR, dual luciferase assays and FISH. After silencing CircGLCE or miR-587, western blotting, immunofluorescence analysis, and flow cytometry were conducted. STAP1 was assessed by RT-qPCR and luciferase assay, and experiments with silenced and overexpressed miR-587 were performed. A rescue experiment was also included. In an IDD rat model, the in vivo effects of overexpressing CircGLCE on IDD were analysed with imaging techniques, TUNEL staining, FISH, western blotting, H&E staining and immunohistochemistry.ResultsCircGLCE was found to stably exist in the cytoplasm of nucleus pulposus (NP) cells. It was downregulated in IDD. Knockdown of CircGLCE promoted apoptosis and induced the expression of matrix-degrading enzymes in NP cells. CircGLCE served as a miR-587 sponge in NP cells. Inhibiting miR-587 counteracted the IDD-enhancing effect caused by silencing CircGLCE. STAP1 served as the miRNA target that mediated the functions of miR-587. Overexpressing CircGLCE alleviated IDD in vivo.ConclusionsCircGLCE attenuates IDD by regulating the apoptosis of NP cells and by regulating ECM degradation through the targeting of miR-587/STAP1. CircGLCE may be a potential therapeutic target for IDD treatments.

scholarly journals The effects of simulated +Gz and microgravity on intervertebral disc degeneration in rabbits

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Di Wu ◽  
Xi Zhou ◽  
Chao Zheng ◽  
Yu He ◽  
Lingjia Yu ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
The Body ◽  
Microgravity Environment ◽  
Control Group ◽  
Group A ◽  
Suspension Model ◽  
Mixed Groups ◽  
Over Time

Abstract The overall objective of this study was to test the hypothesis that +Gz (hypergravity/positive acceleration) and microgravity can both aggravate intervertebral disc degeneration (IVDD). Due to +Gz and microgravity, many pilots develop IVDD. However, the lack of animal models of IVDD under conditions of simulated +Gz and microgravity has hampered research on the onset and prevention of IVDD. Rabbits were randomly allotted to a control group, microgravity group, +Gz group, or mixed (+Gz + microgravity) group. A tail-suspension model was utilized to simulate a microgravity environment and an animal centrifuge to mimic +Gz conditions. After exposure to the above conditions for 4, 8, and 24 weeks, the body weights (BW) of animals in the control group gradually increased over time, while those of animals in the microgravity and mixed groups both decreased (p < 0.001). As compared with the control group, the proteoglycan content of animals in the other three groups was significantly reduced (F = 192.83, p < 0.001). The imageological, histopathological, and immunohistochemical changes to the L6–S1 intervertebral disc samples suggests that the effects of +Gz and microgravity can aggravate IVDD over time. The mixed effects of +Gz and microgravity had the greatest effect on degeneration and +Gz had a particularly greater effect than microgravity.

scholarly journals Circular RNAs in nucleus pulposus cell function and intervertebral disc degeneration

2019 ◽  
Vol 52 (6) ◽  
Author(s):  
Zheng Li ◽  
Xin Chen ◽  
Derong Xu ◽  
Shugang Li ◽  
Matthew T. V. Chan ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Cell Function ◽  
Nucleus Pulposus Cell ◽  
Circular Rnas

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 Circular RNAs in Intervertebral Disc Degeneration: An Updated Review

2022 ◽  
Vol 8 ◽  
Author(s):  
Derong Xu ◽  
Xuexiao Ma ◽  
Chong Sun ◽  
Jialuo Han ◽  
Chuanli Zhou ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Medical Condition ◽  
Nucleus Pulposus Cell ◽  
Major Type ◽  
Circular Rnas ◽  
Public Health Burden ◽  
Matrix Deposition ◽  
Common Medical Condition

Low back pain, a common medical condition, could result in severe disability and inflict huge economical and public health burden. Its pathogenesis is attributed to multiple etiological factors, including intervertebral disc degeneration (IDD). Emerging evidence suggests that circular RNAs (circRNAs), a major type of regulatory non-coding RNA, play critical roles in cellular processes that are pertinent to IDD development, including nucleus pulposus cell proliferation and apoptosis as well as extracellular matrix deposition. Increasing number of translational studies also indicated that circRNAs could serve as novel biomarkers for the diagnosis of IDD and/or predicting its clinical outcomes. Our review aims to discuss the recent progress in the functions and mechanisms of newly discovered IDD-related circRNAs.

scholarly journals Emerging evidence on noncoding-RNA regulatory machinery in intervertebral disc degeneration: a narrative review

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Hao-Yu Guo ◽  
Ming-Ke Guo ◽  
Zhong-Yuan Wan ◽  
Fang Song ◽  
Hai-Qiang Wang
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Intervertebral Disc Degeneration ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Circular Rnas ◽  
Form Complex ◽  
Underlying Mechanisms

AbstractIntervertebral disc degeneration (IDD) is the most common cause of low-back pain. Accumulating evidence indicates that the expression profiling of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs), are different between intervertebral disc tissues obtained from healthy individuals and patients with IDD. However, the roles of ncRNAs in IDD are still unclear until now. In this review, we summarize the studies concerning ncRNA interactions and regulatory functions in IDD. Apoptosis, aberrant proliferation, extracellular matrix degradation, and inflammatory abnormality are tetrad fundamental pathologic phenotypes in IDD. We demonstrated that ncRNAs are playing vital roles in apoptosis, proliferation, ECM degeneration, and inflammation process of IDD. The ncRNAs participate in underlying mechanisms of IDD in different ways. MiRNAs downregulate target genes’ expression by directly binding to the 3′-untranslated region of mRNAs. CircRNAs and lncRNAs act as sponges or competing endogenous RNAs by competitively binding to miRNAs and regulating the expression of mRNAs. The lncRNAs, circRNAs, miRNAs, and mRNAs widely crosstalk and form complex regulatory networks in the degenerative processes. The current review presents novel insights into the pathogenesis of IDD and potentially sheds light on the therapeutics in the future.

scholarly journals Circ_0004354 might compete with circ_0040039 to induce NPCs death and inflammatory response by targeting miR-345-3p-FAF1/TP73 axis in intervertebral disc degeneration

2022 ◽  
Vol 2022 ◽  
pp. 1-21
Author(s):  
Yongjin Li ◽  
Xiaojing Wu ◽  
Jianhua Li ◽  
Lilong Du ◽  
Xuke Wang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Pathological Process ◽  
Circular Rnas ◽  
Nucleus Pulposus Cells ◽  
Promising Therapeutic Target ◽  
Pathological Mechanism ◽  
Ecm Degradation

The abnormal function of nucleus pulposus cells (NPCs) plays a crucial role in the pathogenesis of intervertebral disc degeneration (IVDD). Recent studies have demonstrated that circular RNAs (circRNAs) are involved in the pathological process of IVDD by regulating NPCs’ function. Nevertheless, the investigation on circRNA-circRNA interaction has not yet been reported. Here, we identified the top upregulated circ_0040039 and circ_0004354 in IVDD, derived from the syntrophin beta 2 gene but had different degrees of biological functions. Accumulating studies have reported PANoptosis is composed of apoptosis, pyroptosis, and necroptosis. Based on this, we think there should be a new pro-inflammatory cell death PAoptosis in the form of apoptosis and pyroptosis. Circ_0004354 might compete with circ_0040039 to induce the development of IVDD by modulating miR-345-3p-FAF1/TP73 axis-mediated PAoptosis, inflammatory response, growth inhibition, and ECM degradation of NPCs. Thus, these findings offer a novel insight into the circRNAs-mediated posttranscriptional regulatory network in IVDD, contributing to further clarification of the pathological mechanism of IVDD to develop a promising therapeutic target for IVDD diseases.

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