scholarly journals Prediction of a Potential Mechanism of Intervertebral Disc Degeneration Based on a Novel Competitive Endogenous RNA Network

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Junshen Huang ◽  
Yuxi Li ◽  
Ziwei Ye ◽  
Ziying Cheng ◽  
Jiajun Huang ◽  
...  

Low back pain which resulted from intervertebral disc degeneration (IDD) is a common health problem that afflicts people all over the world. Due to the lack of an overall understanding of the molecular interactions involved in IDD, we hope to better understand the pathogenetic mechanisms that drive the degenerative process. The purpose of this study is to obtain mRNAs, miRNAs, lncRNAs, and circRNAs associated with IDD gained from public databases and to establish an interaction network. According to the results of microarray analysis and bioinformatics analysis from the contrast of IDD and normal nucleus pulposus tissues, a total of 49 mRNAs, 10 miRNAs, 30 lncRNAs, and 4 circRNAs were obtained and a lncRNA/circRNA–miRNA–mRNA interaction network was constructed. NEAT1–miR-5100–COL10A1 and miR663AHG/HEIH/hsa-circ-0003600–miR-4741–HAS2/HYAL1/LYVE1 might be potential interaction axes of the molecular mechanism in IDD. The increased expression of NEAT1 might inhibit miR-5100 and subsequently upregulate the expression of COL10A1, which leads to IDD, while the increased expression of miR663AHG/HEIH/hsa-circ-0003600 might inhibit miR-4741 and indirectly upregulate HAS2/HYAL1/LYVE1, and leads to the protection from IDD. More interaction axes are to be exploited to provide theoretical bases for further study on IDD.

2020 ◽  
Author(s):  
Hosni Cherif ◽  
Daniel G Bisson ◽  
Matthew Mannarino ◽  
Oded Rabau ◽  
Jean A Ouellet ◽  
...  

2017 ◽  
Vol 27 (1) ◽  
pp. 116-126 ◽  
Author(s):  
Qiuqian Wu ◽  
Jason H. Huang

OBJECTIVELumbar intervertebral disc degeneration, an age-related process, is a major cause of low-back pain. Although low-back pain is a very common clinical problem in the aging population, no effective treatment is available, largely owing to lack of understanding of the molecular mechanisms underlying disc degeneration. The goal of this study was to characterize how ectopic expression of Smurf2 driven by the collagen Type II alpha 1 (Col2a1) promoter alters disc cell phenotype and associated cellular events, matrix synthesis, and gene expression during disc degeneration in mice.METHODSTo characterize how ectopic expression of Smurf2 in Col2a1-promoter working cells affects the disc degeneration process, the authors performed histological and immunohistochemical analysis of lumbar spine specimens harvested from wild-type (WT) and Col2a1-Smurf2 transgenic mice at various ages (n ≥ 6 in each age group). To elucidate the molecular mechanism underlying Smurf2-mediated disc degeneration, the authors isolated cells from WT and Col2a1-Smurf2 transgenic lumbar intervertebral discs and performed Western blot and real-time RT-PCR (reverse transcription polymerase chain reaction) to examine the protein and mRNA levels of interesting targets.RESULTSThe authors demonstrated that approximately 30% of WT mice at 10–12 months of age had started to show disc degeneration and that the disc degeneration process was accelerated by 3–6 months in Col2a1-Smurf2 transgenic mice. Chondrocyte-like cell proliferation, maturation, and fibrotic tissue formation in the inner annulus were often accompanied by fibroblast-to-chondrocyte differentiation in the outer annulus in transgenic discs. The chondrocyte-like cells in transgenic discs expressed higher levels of connective tissue growth factor (CTGF) than were expressed in WT counterparts.CONCLUSIONSThe findings that ectopic expression of Smurf2 driven by the Col2a1 promoter accelerated disc degeneration in Col2a1-Smurf2 transgenic mice, and that higher levels of CTGF protein and mRNA were present in Col2a1-Smurf2 transgenic discs, indicate that Smurf2 accelerates disc degeneration via upregulation of CTGF.


2016 ◽  
Vol 25 (9) ◽  
pp. 2849-2855 ◽  
Author(s):  
Steffen Folkvardsen ◽  
Erland Magnussen ◽  
Jaro Karppinen ◽  
Juha Auvinen ◽  
Rasmus Hertzum Larsen ◽  
...  

2021 ◽  
Vol 11 (3) ◽  
pp. 817-821
Author(s):  
Peng Tang ◽  
Jingtao Xu ◽  
Wei Liu ◽  
Yu Li ◽  
Wei Fan ◽  
...  

The advantage and value of magnetic resonance (MR)-ultra-short echo time (UTE) technique in the displaying the structures of degenerative intervertebral discs were observed through evaluating the lumbar disc degeneration in the axial plane by conventional MR image and MR-UTE technique. A total of 160 examinees screened by inclusion and exclusion criteria were enrolled, and a total of 800 intervertebral disks were involved, and the degree of intervertebral disc degeneration was classified by conventional MR image classification method. After the first echo image of MR-UTE technique was integrated with the contour, the image entered UTE cartilage endplate, fibrous ring and osseous endplate. The integrity of the intervertebral disc from the above and below the intervertebral disc and the correlation of the structural endplate with the integrities of cartilage endplate, fibrous ring and osseous endplate under double echo sequence were analyzed, and the correlation analysis of the two categorical variables was conducted using rank correlation analysis. Under the MR-UTE sequence, there was no statistical significant difference in structural integrity constituent ratio (intact structure only on one side, incomplete structure on both side) between the non-low back pain group and the low back pain group (P > 0.05), the proportion of complete structure disappearance was lowest, and the proportion of partial structure disappearance was highest; there was a significant difference in the structural integrity of fibrous ring between the non-low back pain group and the low back pain group (P < 0.05), there was a statistical significant difference in structural integrity of fibrous rings between the two groups (P < 0.05); there was a statistical significant difference in pain degree between the partial structure disappearance group and the complete structure disappearance group (P < 0.05). There was no significant difference in pain degree between the groups (intact structure only on one side and incomplete structure on both side); conventional MR images showed no significant difference in the intervertebral disc degeneration degree between the non-low back pain group and low back pain group (P > 0.05), and the intervertebral disc degeneration degree had no significant correlation with the lower back pain. MR-UTE sequence and T2WI sequence showed that there was a correlation between different intervertebral disc degeneration degrees and the structural integrity distributions of cartilage endplate, osseous endplate and fibrous rings in two groups of patients with or without low back pain (P < 0.05). Whether low back pain exists or not has little effect on the intervertebral disc degeneration degree on T2WI. MR-UTE double echo sequence scan reveals that the intervertebral disc degeneration degree is positively related to the integrity and integrity distribution of cartilage endplate, fibrous ring and bone endplate.


2018 ◽  
Vol 10 (1) ◽  
pp. 1 ◽  
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya

BACKGROUND: Low back pain (LBP) mostly caused by disc degeneration, reflects to a tremendous of health care system and economy. More knowledge about these underlying pathologies will improve the opportunities that may represent critical therapeutic targets.CONTENT: Basic research is advancing the understanding of the pathogenesis and management of LBP at the molecular and genetic levels. Cytokines such as matrix metalloproteinases, phospholipase A2, nitric oxide, and tumor necrosis factor-α are thought to contribute to the development of LBP. Mesenchymal stem cells (MSCs) transplant to cartilage-like cells and secrete extracellular matrix and encourage nucleus pulposus (NP) cell activity inhibiting NP cell apoptosis, together with some chemical mediators such as cytokines and growth factors become a safe and effective new strategy for intervertebral disc degeneration (IDD) treatment and regeneration.SUMMARY: IDD occurs where there is a loss of homeostatic balance with a predominantly catabolic metabolic profile. A basic understanding of the molecular changes occurring in the degenerating disc is important for practicing clinicians to help them to inform patients to alter lifestyle choices, identify beneficial or harmful supplements, or offer new biologic, genetic, or stem cell therapies.KEYWORDS: low back pain (LBP), intervertebral disc (IVD), degeneration, nucleus pulposus (NP), annulus fibrosus (AF), extracellular matrix (ECM), genetic, stem cells


2020 ◽  
Author(s):  
Ting-Sheng Wu ◽  
Shao-Yong Fan ◽  
Bin Zhang ◽  
Zhi-Qiang Tao ◽  
Hong Hua ◽  
...  

Abstract Background: Intervertebral disc degeneration (IDD) is the important cause of low back pain. Excessive apoptosis of intervertebral disc cells is the primary cause of IDD. BNIP3 is a member of Bcl-2 family and is widely involved in cell autophagy and apoptosis. However, the roles and mechanisms of BNIP3 in intervertebral disc cell autophagy and apoptosis are unclear.Results: In this study, the primary rat intervertebral disc cells were prepared and applied to study the effect of BNIP3 overexpression on their autophagy and apoptosis. RT-PCR and western blotting assay showed that BNIP3 overexpression significantly up-regulated the expression of autophagy and pro-apoptotic related proteins, including HIF-1α, Apaf-1, cleaved caspase 3, LC-3 and Beclin-1, while down-regulated the expression of anti-apoptotic protein Bcl-2. Subsequent cell staining detection of autophagy and apoptosis showed that BNIP3 overexpression significantly increased the autophagy and apoptosis of rat intervertebral disc cells. Furthermore, BNIP3 interference assay revealed that the effects of BNIP3 overexpression can be reversed by BNIP3 interference. Conclusions: The above findings suggested that BNIP3 enhanced autophagy of intervertebral disc cells and further triggered the apoptosis of intervertebral disc cells, eventually led to the development of intervertebral disc degeneration.


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