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Integrative Bioinformatics Analysis Reveals Potential Gene Biomarkers and Analysis of Function in Human Degenerative Disc Annulus Fibrosus Cells.

ABSTRACT: Low back pain is a major cause of disability worldwide. Although numerous potential biomarkers for the early diagnosis or treatment of intervertebral disc degeneration (IDD) have been identified subsequent to the development of molecular biology technologies, the mechanisms of IDD remain unknown. Published studies found the unbalance of anabolism and catabolism of annulus fibrosus (AF) played an important role in it. The present study was aimed to identify the potential targets and signaling pathways of IDD, through the combined analysis of differential expression and based on the Gene Expression Omnibus (GEO) dataset from NCBI. PPI Networks Analysis indicated that MMP2 and AGE-RAGE signaling pathway and estrogen signaling pathway may play important roles in initiation and development of IDD. This study forecasted the pathogenesis molecular mechanism of IDD and the potential prognostic and diagnostic biomarkers, but we need to make further molecular biological experiments to confirm our assumptions.

SUBMITTER: Xunlu Y

PROVIDER: S-EPMC6409044 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Integrative Bioinformatics Analysis Reveals Potential Gene Biomarkers and Analysis of Function in Human Degenerative Disc Annulus Fibrosus Cells.

Xunlu Yin Y Minshan Feng F Liguo Zhu Z Jiawen Zhan Z Xu Wei W Jie Yu Y Shangquan Wang W He Yin Y Long Liang L Tao Han H Xuepeng Li L

BioMed research international 20190221

Low back pain is a major cause of disability worldwide. Although numerous potential biomarkers for the early diagnosis or treatment of intervertebral disc degeneration (IDD) have been identified subsequent to the development of molecular biology technologies, the mechanisms of IDD remain unknown. Published studies found the unbalance of anabolism and catabolism of annulus fibrosus (AF) played an important role in it. The present study was aimed to identify the potential targets and signaling pat ...[more]

PMID: 30915367

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Project description:Degenerative disc disease (DDD) is accompanied by structural changes in the intervertebral discs (IVD). Extra-cellular matrix degradation of the annulus fibrosus (AF) has been linked with degeneration of the IVD. Collagen is a vital component of the IVD. Collagen hybridizing peptide (CHP) is an engineered protein that binds to degraded collagen, which we used to quantify collagen damage in AF. This method was used to compare AF samples obtained from donors with no DDD to AF samples from patients undergoing surgery for symptomatic DDD. Fresh AF tissue was embedded in an optimal cutting temperature compound and cryosectioned at a thickness of 8 μm. Hematoxylin and Eosin staining was performed on sections for general histomorphological assessment. Serial sections were stained with Cy3-conjugated CHP and the mean fluorescence intensity and areal fraction of Cy3-positive staining were averaged for three regions of interest (ROI) on each CHP-stained section. Increases in mean fluorescence intensity (p = 0.0004) and percentage of positively stained area (p = 0.00008) with CHP were detected in DDD samples compared to the non-DDD samples. Significant correlations were observed between mean fluorescence intensity and percentage of positively stained area for both non-DDD (R = 0.98, p = 5E-8) and DDD (R = 0.79, p = 0.0012) samples. No significant differences were detected between sex and the lumbar disc level subgroups of the non-DDD and DDD groups. Only tissue pathology (non-DDD versus DDD) influenced the measured parameters. No three-way interactions between tissue pathology, sex, and lumbar disc level were observed. These findings suggest that AF collagen degradation is greater in DDD samples compared to non-DDD samples, as evidenced by the increased CHP staining. Strong positive correlations between the two measured parameters suggest that when collagen degradation occurs, it is detected by this technique and is widespread throughout the tissue. This study provides new insights into the structural alterations associated with collagen degradation in the AF that occur during DDD.

Dataset Information

Integrative Bioinformatics Analysis Reveals Potential Gene Biomarkers and Analysis of Function in Human Degenerative Disc Annulus Fibrosus Cells.

Publications

Integrative Bioinformatics Analysis Reveals Potential Gene Biomarkers and Analysis of Function in Human Degenerative Disc Annulus Fibrosus Cells.

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