scholarly journals Age-related reduction in the expression of FOXO transcription factors and correlations with intervertebral disc degeneration

2017 ◽  
Vol 35 (12) ◽  
pp. 2682-2691 ◽  
Author(s):  
Oscar Alvarez-Garcia ◽  
Tokio Matsuzaki ◽  
Merissa Olmer ◽  
Koichi Masuda ◽  
Martin K. Lotz
Keyword(s):  
Transcription Factors ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Age Related ◽  
Foxo Transcription Factors

scholarly journals Ectopic expression of Smurf2 and acceleration of age-related intervertebral disc degeneration in a mouse model

2017 ◽  
Vol 27 (1) ◽  
pp. 116-126 ◽  
Author(s):  
Qiuqian Wu ◽  
Jason H. Huang
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Transgenic Mice ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Ectopic Expression ◽  
Cell Phenotype ◽  
Low Back ◽  
Age Related

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.

scholarly journals Identification of Key Genes and Pathways Associated With Pathogenesis of Intervertebral Disc Degeneration by Integrated miRNA-mRNA Network Analysis

2021 ◽  
Author(s):  
Tao Lan ◽  
Ning-dao Li ◽  
Zhe Shen ◽  
Xiao-sheng Chen ◽  
Shi-yu Hu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Intervertebral Disc ◽  
Signaling Pathway ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Target Genes ◽  
Functional Enrichment ◽  
Receptor Interaction ◽  
Critical Pathways ◽  
Underlying Mechanisms

Abstract Background: Intervertebral disc degeneration (IDD) is one of the most common cause of low back pain. Previous studies have suggested that miRNAs are associated with the pathogenesis of IDD. However, the underlying mechanisms remain unclear based on inconsistent results of available literatures. In addition, integrated miRNA-mRNA comprehensive analysis is limited. Material/Methods: In this study, we investigated the profiles of differentially expressed miRNAs (DEMIs) and mRNAs (DEGs) and constructed a miRNA-mRNA regulatory network. First, transcription factors and target genes of DEMIs were predicted. Then, an intersection between DEMIs predicted genes and DEGs were performed to screen out the most significant differential expressed common genes. Results: A total of 65 DEMIs and 61 common target genes were identified from datasets. Functional enrichment analysis showed that most genes were mainly involved in extracellular matrix organization and extracellular structure organization. Furthermore, DEGs were primarily enriched in PI3K−Akt signaling pathway, ECM−receptor interaction, focal adhesion and p53 signaling pathway, indicating that these pathways may be the critical pathways.Conclusions: In summary, several important miRNAs, as well as their related target genes and transcription factors in the pathogenesis of IDD were identified from our bioinformatic analysis, which may provide insights into underlying mechanisms and offer potential target genes for the treatment of IDD.

scholarly journals Association of interleukin 2, interleukin 12, and interferon-γ with intervertebral disc degeneration in Iranian population

2020 ◽  
Author(s):  
Sara Hanaei ◽  
Sina Abdollahzade ◽  
Maryam Sadr ◽  
Mohammad Hossein Mirbolouk ◽  
Ehsan Fattahi ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Interleukin 2 ◽  
Interleukin 12 ◽  
Healthy Controls ◽  
Eligibility Criteria ◽  
Age Related ◽  
Ifn Γ

Abstract Background: Intervertebral disc degeneration (IVDD) is an age-related degenerative disease, presenting with low back pain or radicular pain. The inflammatory changes would occur in discs in the process of IVDD. Therefore, the inflammatory and anti-inflammatory cytokines, as well as their respective genes, have been proposed to play roles in pathophysiology of disease. This study has been conducted to elucidate the role of IL-2, IL-12, and IFN-γ single nucleotide polymorphisms (SNP) in this disease.Method: 76 patients who were diagnosed with IVDD and 140 healthy controls who complied with eligibility criteria were included. A total volume of 5cc peripheral blood was obtained from each participant to investigate the IL-2 +166G/T, IL-2 -330G/T, IL-12 -1188A/C, and IFN-γ +847A/T SNPs through PCR-SSP method.Results: The ‘TG’ and ‘TT’ genotypes of IL-2 -330G/T polymorphism were significantly more common among patients and healthy controls respectively. The ‘GT’ and ‘TT’ haplotypes of IL-2 (comprised of -330G/T, and +166G/T SNPs) were also more common among patients and controls respectively.Conclusion: This study indicated the significant role of IL-2 genotypes and haplotypes in IVDD. These SNPs were differently distributed in patients and controls. Therefore, alteration in the structure of IL-2 gene could play an important role in pathophysiology of IVDD.

scholarly journals Loss of tenomodulin expression is a risk factor for age‐related intervertebral disc degeneration

Aging Cell ◽  
2020 ◽  
Vol 19 (3) ◽  
Author(s):  
Dasheng Lin ◽  
Paolo Alberton ◽  
Manuel Delgado Caceres ◽  
Carina Prein ◽  
Hauke Clausen‐Schaumann ◽  
...  
Keyword(s):  
Risk Factor ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Age Related
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