Expression data between human degenerative and non-degenerative intervertebral discs
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE34095 | GEO | 2012/06/01
SECONDARY ACCESSION(S): PRJNA149897
REPOSITORIES: GEO
Similar Datasets
Project description:Disc Degeneration is a multifactorial disease which cause severe constant chronic pain. The development of disc degeneration could involve both genetic and environmental factors, so it's important to elucidate the difference in gene expression profiles between degenerative and non-degenerative discs from elderly patients and younger patients, respectively. Affymetrix GeneChip Human Genome U133A Array was used to derive gene expression profiles and identified genes that would express at significantly different levels between degenerative and non-degenerative samples. Human intervertebral disc tissues were harvested from elderly and younger patients with degenerative disc disease and adolescent idiopathic scoliosis, respectively, for RNA extraction and hybridization on Affymetrix microarrays. One degenerative sample was compared to one non-degenerative sample in the same microarray run, and comparative analyses were performed in triplicate. Gene whose expression levels varied across the samples with a log ratio >0.5 or <-0.5 were selected as the genes related to disc degeneration.
2012-05-31 | E-GEOD-34095 | biostudies-arrayexpress
Project description:Research on disc degeneration has been heterogeneous in their use of control discs used for comparison with diseased discs. Discs from scoliosis, cadavers and voluntary organ donors are the common controls used in intervertebral disc research. In order to find out the ideal control among these discs, the characters of scoliotic discs and discs from MRI normal voluntary organ donors controls used in disc research has been analysed using proteomics and to establish 'True Controls' that can be utilized for future Intervertebral disc (IVD) research.
2022-06-09 | PXD018968 | Pride
Project description:Intervertebral Disc (IVD) degeneration leading to Low back pain (LBP) is the most common musculoskeletal disorder. Lack of knowledge on the intricate homeostatic mechanisms necessitates proteomic characterisation of a normal human IVD to understand the biological process and unravel the pathomechanisms of degenerative disc disease (DDD). In this study, we employed proteomic approach coupled with tandem mass-spectrometry to derive the comprehensive list of proteins expressed in true biologically normal control discs. This would serve as the basis for identifying the interacting molecules participating in significant biological processes and pathways disrupted during aging and degeneration.
2021-09-09 | PXD016560 | Pride
Project description:Low back pain is a major cause of disability especially for people between 20 and 50 years of age. As a costly healthcare problem, it imposes a serious socio-economic burden. Current surgical therapies have considerable drawbacks and fail to replace the normal disc in facilitating spinal movements and absorbing load. Therefore, the focus of regenerative medicine is on identifying biomarkers and signalling pathways to improve our understanding about the cascades of disc degeneration and allow for the design of specific therapies. We hypothesized that comparing microarray profiles from degenerative and non-degenerative discs will lead to the identification of dysregulated signalling and pathophysiological targets. Microarray data sets were generated from human annulus fibrosus cells and analysed using IPA ingenuity pathway analysis system. Gene expression values were validated by qRT-PCR, and respective proteins were identified by immunohistochemistry. Microarray analysis revealed 17 dysregulated molecular markers and various dysregulated cellular functions, including cell proliferation and inflammatory response, in the human degenerative annulus fibrosus. The most significant canonical pathway induced in degenerative annulus fibrosus was found to be the interferon signalling pathway. In conclusion, this study indicates interferon-alpha signalling pathway activation with IFIT3 and IGFBP3 up-regulation which may affect cellular function in human degenerative disc. 48 samples of intervertebral disc tissue - annulus fibrosus and nucleus pulposus - displaying varying degrees (grades) of degeneration
2015-10-23 | E-GEOD-70362 | biostudies-arrayexpress
Project description:It has been shown that the divergence of NPCs plays an important role in the progression of intervertebral disc degeneration (IVDD). We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of NPCs in the IVDD.
2023-10-30 | GSE244889 | GEO
Project description:Asporin, also known as periodontal ligament-associated protein 1 (PLAP1), is a member of the family of small leucine-rich proteoglycan (SLRP) family. It is present within the cartilage extracellular matrix (ECM), and is reported have a genetic association with osteoarthritis. Its D14 allele has recently been found to be associated with lumbar disc degeneration in Asian subjects. There have been no studies, however, of this gene’s normal immunohistochemical localization within the human intervertebral disc, nor of expression levels in Caucasian individuals with disc degeneration. Studies were approved by our human subjects Institutional Review Board. Methods included immunohistochemical localization of asporin in the disc of humans and the sand rat (a small rodent with spontaneous age-related disc degeneration), and Affymetrix microarray analysis of asporin gene expression in vivo and in vitro. mmunohistochemical studies of human discs revealed that some, but not all, cells of the outer annulus expressed asporin. Fewer cells in the inner annulus contained asporin, and it was rarely present in cells in the nucleus pulposus. Similar patterns were found for the presence of asporin in lumbar discs of sand rats. Substantial relative gene expression levels were seen for asporin in both disc tissue and in annulus cells grown in three-dimensional culture. More degenerate human discs (Thompson grade 4) showed higher expression levels of asporin than did less degenerate (grade 1, 2 and 3) discs, p = 0.004. In the discs of Caucasian subjects studied here, and in the sand rat, greater immunolocalization levels were found in the outer compared to inner annulus. Localization was rare in the nucleus. Gene expression studies showed greatest expression of asporin in the more degenerate human discs in vivo. Disc Tissue samples were obtained via the National Cancer Institute Cooperative Tissue Network (CHTN) as well as surgical disc procedures performed on patients with herniated discs and degenerative disc disease. Tissue was fixed and paraffin embedded. Standard laser capture microdissection (LCM) techniques were used to collect the cells from which total RNA was isolated and analyzed via microarray. Based on the Thompson scouring system, unhealthy discs (grade 4) were compared to healthy discs (grades 2,3).
2009-03-24 | E-GEOD-15227 | biostudies-arrayexpress
Project description:Low back pain is a major cause of disability especially for people between 20 and 50 years of age. As a costly healthcare problem, it imposes a serious socio-economic burden. Current surgical therapies have considerable drawbacks and fail to replace the normal disc in facilitating spinal movements and absorbing load. Therefore, the focus of regenerative medicine is on identifying biomarkers and signalling pathways to improve our understanding about the cascades of disc degeneration and allow for the design of specific therapies. We hypothesized that comparing microarray profiles from degenerative and non-degenerative discs will lead to the identification of dysregulated signalling and pathophysiological targets. Microarray data sets were generated from human annulus fibrosus cells and analysed using IPA ingenuity pathway analysis system. Gene expression values were validated by qRT-PCR, and respective proteins were identified by immunohistochemistry. Microarray analysis revealed 17 dysregulated molecular markers and various dysregulated cellular functions, including cell proliferation and inflammatory response, in the human degenerative annulus fibrosus. The most significant canonical pathway induced in degenerative annulus fibrosus was found to be the interferon signalling pathway. In conclusion, this study indicates interferon-alpha signalling pathway activation with IFIT3 and IGFBP3 up-regulation which may affect cellular function in human degenerative disc.
2015-10-23 | GSE70362 | GEO
Project description:Purpose: Degenerative changes of the intervertebral disc are a leading cause of back pain and disability worldwide. However, precise mechanisms driving the initiation and progression of pathology have remained elusive. We find that adhesion G-protein coupled receptor Adgrg6 plays a critical role in maintaining postnatal intervertebral disc homeostasis. The goal of this study is to uncover early molecular changes in Adgrg6-defeicnet intervertebral discs prior to overt histopathology. Methods: Intervertebral disc mRNA profiles of 20-day-old wild type and Col2Cre; Adgrg6f/f mutant mice were generated by deep sequencing in triplicates. Cutadapt and perl scripts were used to remove the reads that contained adaptor contamination, low quality bases and undetermined bases. Then sequence quality was verified using FastQC. We used HISAT2 to map reads to the genome of Mus Musculus (GRCm38.88). The mapped reads of each sample were assembled using StringTie. Then, all transcriptomes from biological samples were merged to reconstruct a comprehensive transcriptome using perl scripts and gffcompare. After the final transcriptome was generated, StringTie and Ballgown was used to estimate the expression levels of all transcripts. StringTie was used to perform expression level for mRNAs by calculating FPKM. The differentially expressed mRNAs were selected with log2 (fold change) >1 or log2 (fold change) <-1 and with statistical significance (p value < 0.05) by R package Ballgown. Results: We found 884 differential expressed genes with statistical significance (p value < 0.05, and with a more stringent cut-off adjusted p value <0.05 and fold-change >2, we observed 42 differential expressed genes. Enriched pathways and biological processes using gene ontology (GO) terms included extracellular matrix, positive regulation of fibroblast proliferation, extracellular matrix structural constituent conferring tensile strength, regulation of tyrosine phosphorylation of STAT protein, and ion transport. We also find significantly increased expression of fibrotic collagens, induced expression of some Suppressor of Cytokine Signaling (SOCS) genes, and dysregulated expression of some components associated with ion transport system. Several of the significantly upregulated genes are associated with biomarkers or risk of lumbar disc degeneration and osteoarthritis in humans or animal models. Conclusions: Our study provides detailed analysis of intervertebral disc transcriptomes from both wild type and Adgrg6-deficient mice, with three biological replicates, prior to overt histopathology. Our transcriptomic analysis demonstrated a robust dysregulation of several important pathways and components of the intervertebral disc homeostasis, including induction of fibrotic gene expression, alteration of ion transport component, as well as changes in some chondrogenic and catabolic factors, prior to the onset of histopathology and disc degeneration. These data strongly suggest that ADGRG6 signaling is a critical factor for the maintenance of healthy gene expression profiles in the IVD.
2019-03-17 | GSE128402 | GEO
Project description:Asporin, also known as periodontal ligament-associated protein 1 (PLAP1), is a member of the family of small leucine-rich proteoglycan (SLRP) family. It is present within the cartilage extracellular matrix (ECM), and is reported have a genetic association with osteoarthritis. Its D14 allele has recently been found to be associated with lumbar disc degeneration in Asian subjects. There have been no studies, however, of this gene’s normal immunohistochemical localization within the human intervertebral disc, nor of expression levels in Caucasian individuals with disc degeneration. Studies were approved by our human subjects Institutional Review Board. Methods included immunohistochemical localization of asporin in the disc of humans and the sand rat (a small rodent with spontaneous age-related disc degeneration), and Affymetrix microarray analysis of asporin gene expression in vivo and in vitro. mmunohistochemical studies of human discs revealed that some, but not all, cells of the outer annulus expressed asporin. Fewer cells in the inner annulus contained asporin, and it was rarely present in cells in the nucleus pulposus. Similar patterns were found for the presence of asporin in lumbar discs of sand rats. Substantial relative gene expression levels were seen for asporin in both disc tissue and in annulus cells grown in three-dimensional culture. More degenerate human discs (Thompson grade 4) showed higher expression levels of asporin than did less degenerate (grade 1, 2 and 3) discs, p = 0.004. In the discs of Caucasian subjects studied here, and in the sand rat, greater immunolocalization levels were found in the outer compared to inner annulus. Localization was rare in the nucleus. Gene expression studies showed greatest expression of asporin in the more degenerate human discs in vivo.
2009-03-24 | GSE15227 | GEO
Project description:Intervertebral disc (IVD) degeneration is often the cause of low back pain. Degeneration occurs with age and is accompanied by extracellular matrix (ECM) depletion, culminating in nucleus pulpous (NP) extrusion and IVD destruction. The changes that occur in the disc with age have been under investigation. However, a thorough study of ECM remodelling is needed, to better understand IVD development and age-associated degeneration. As so, iTRAQ LC-MS/MS analysis of foetus, young and old bovine NPs, was used to define the NP matrisome. The enrichment of Collagen XII and XIV in foetus, Fibronectin and Prolargin in elder samples and Collagen XI in young ones was independently validated. This study provides the first matrisome database of healthy discs during development and ageing, which is key to determine the pathways and processes that maintain disc homeostasis. The factors identified may help to explain age-associated IVD degeneration or constitute putative effectors for disc regeneration.
2017-09-25 | PXD005616 | Pride