Bioinformatics analysis reveals different gene expression patterns in the annulus fibrosis and nucleus pulpous during intervertebral disc degeneration

Wang, Yi; Jiang, Ling; Dai, Guogang; Li, Shengwu; Mu, Xiaoyuan

doi:10.3892/etm.2018.6884

Cited by 14 publications

(13 citation statements)

References 54 publications

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“…Both grouping methods have pros and cons. Second, we have performed several other similar studies [ 11 , 45 , 46 ], but the results of these studies and the present study were not much the same. All of our studies are cross-sectional studies, and due to the limitations of a cross-sectional study, the results are largely affected by the conditions at the time of the study.…”

Section: Discussioncontrasting

confidence: 54%

Microarray analysis reveals an inflammatory transcriptomic signature in peripheral blood for sciatica

et al. 2021

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Background Although the pathology of sciatica has been studied extensively, the transcriptional changes in the peripheral blood caused by sciatica have not been characterized. This study aimed to characterize the peripheral blood transcriptomic signature for sciatica. Methods We used a microarray to identify differentially expressed genes in the peripheral blood of patients with sciatica compared with that of healthy controls, performed a functional analysis to reveal the peripheral blood transcriptomic signature for sciatica, and conducted a network analysis to identify key genes that contribute to the observed transcriptional changes. The expression levels of these key genes were assessed by qRT-PCR. Results We found that 153 genes were differentially expressed in the peripheral blood of patients with sciatica compared with that of healthy controls, and 131 and 22 of these were upregulated and downregulated, respectively. A functional analysis revealed that these differentially expressed genes (DEGs) were strongly enriched for the inflammatory response or immunity. The network analysis revealed that a group of genes, most of which are related to the inflammatory response, played a key role in the dysregulation of these DEGs. These key genes are Toll-like receptor 4, matrix metallopeptidase 9, myeloperoxidase, cathelicidin antimicrobial peptide, resistin and Toll-like receptor 5, and a qRT-PCR analysis validated the higher transcript levels of these key genes in the peripheral blood of patients with sciatica than in that of healthy controls. Conclusion We revealed inflammatory characteristics that serve as a peripheral blood transcriptomic signature for sciatica and identified genes that are essential for mRNA dysregulation in the peripheral blood of patients with sciatica.

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Section: Discussioncontrasting

confidence: 54%

Microarray analysis reveals an inflammatory transcriptomic signature in peripheral blood for sciatica

et al. 2021

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“…MMP-1 is a type of collagenase belonging to the MMP family that specifically degrades collagens in the IVDs. Higher MMP-1 levels have been associated with severe IVD degeneration in terms of gene expression [Vo et al, 2013;Deng et al, 2015;Wang et al, 2018;Zhang et al, 2018]; however, changes in MMP-1 concentrations in IVD tissue remain to be evaluated.…”

Section: Introductionmentioning

confidence: 99%

Human Levels of MMP-1 in Degenerated Disks Can Be Mitigated by Signaling Peptides from Mesenchymal Stem Cells

Hingert

Nawilaijaroen

Ekström

et al. 2020

Cells Tissues Organs

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Degradation of extracellular matrix (ECM) in intervertebral disks (IVDs) during IVD degeneration plays a vital role in low back pain (LBP). In healthy IVDs, synthesis and degradation of ECM are kept in balance by matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs. MMPs are enzymes responsible for ECM degradation, and their expression levels are known to increase in degenerated disks. However, the exact pathophysiological concentration of MMP-1 in the degenerated disks of patients with chronic LBP has not been reported previously. Factors secreted by human mesenchymal stem cells (hMSCs) have shown positive results in cell therapy of degenerated disks. The aim of this study was to investigate the pathophysiological MMP-1 concentration (in ng/mL) in degenerated disk tissue and to evaluate if conditioned media (CM) from hMSCs could mitigate the effects of MMP-1 at the detected levels in a 3D in vitro disk cell (DC) pellet model. Tissue levels of MMP-1 were quantified in disk tissue collected from 6 chronic LBP patients undergoing surgery. DC pellet cultures were performed to investigate the effects of MMP-1 alone and the effects of conditioned media (CM) in the presence of MMP-1. MMP-1 was introduced in the pellets on day 14 at concentrations of 5, 50, or 100 ng/mL. The pellets were harvested on day 28 and evaluated for cell viability, proliferation, and ECM production. The mean concentration of MMP-1 in disk tissue was 151 ng/mL. Results from pellet cultures demonstrated a higher number of viable cells, glycosaminoglycan production, and ECM accumulation in the CM group even in the presence of MMP-1 compared to the controls. However, the level decreased with increasing MMP-1 concentration. The results demonstrated that CM has the ability to mitigate matrix degradation property of MMP-1 up to 50 ng/mL suggesting that CM could potentially be used to treat early stages of disk degeneration.

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“…At present, endoscopic lumbar discectomy is the common treatment method for IDD. However, this method may lead to recurrence of the disease following surgery (6,7). At present, no effective preventative strategy and therapeutic method has been reported for treating IDD, due to the diversity and the unclear cause of low back pain.…”

Section: Introductionmentioning

confidence: 99%

miR‑222 induces apoptosis in human intervertebral disc nucleus pulposus cells by targeting Bcl‑2

Wang

Zhang

et al. 2019

Mol Med Report

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intervertebral disc degeneration (idd) is characterized by abnormal induction of apoptosis in intervertebral disc nucleus pulposus (nP) cells. Previous studies indicated that mir-222 was upregulated in patients with rheumatoid arthritis. However, the effects of mir-222 in idd remain unclear. The present study aimed to demonstrate the role of mir-222 in nP cells. The levels of mir-222 in patients with idd were measured by reverse transcription-quantitative Pcr. cell counting Kit-8 and western blotting assays were used to detect cell proliferation and apoptosis-associated protein levels, respectively. in addition, luciferase reporter assays were performed to validate the predicted target genes of miR-222. miR-222 was significantly upregulated in patients with idd. overexpression of mir-222 inhibited cell proliferation and induced cell apoptosis. Moreover, overexpression of mir-222 resulted in an upregulation in the levels of Bax and cleaved caspase 3, and a downregulation in the levels of Bcl-2 in nP cells. The luciferase reporter assays demonstrated that Bcl-2 is a target of mir-222. Furthermore, overexpression of mir-222 increased the levels of cytochrome c, apoptotic protease activating factor-1 and cleaved caspase 9 in nP cells. conversely, downregulation of mir-222 could promote the proliferation of nP cells. The present data demonstrated that mir-222 induced apoptosis in nP cells by directly targeting Bcl-2. Therefore, mir-222 may act as a potential therapeutic target for the treatment of idd.

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Bioinformatics analysis reveals different gene expression patterns in the annulus fibrosis and nucleus pulpous during intervertebral disc degeneration

Cited by 14 publications

References 54 publications

Microarray analysis reveals an inflammatory transcriptomic signature in peripheral blood for sciatica

Microarray analysis reveals an inflammatory transcriptomic signature in peripheral blood for sciatica

Human Levels of MMP-1 in Degenerated Disks Can Be Mitigated by Signaling Peptides from Mesenchymal Stem Cells

miR‑222 induces apoptosis in human intervertebral disc nucleus pulposus cells by targeting Bcl‑2

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