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Revisiting the microRNA expression profiling of human intervertebral disc degeneration (IDD)

ABSTRACT: MicroRNA expression profiling of human nucleus pulposus derived from patients with IDD in comparison with those derived from cadaveric disc as normal control. We have identified the expression profiles of miRNAs in IDD using scoliotic nucleus pulposus as controls (GSE19943). It is noteworthy that scoliotic discs are not strictly normal discs. Therefore, the microRNA expression profiles were revisited using normal discs as control.

ORGANISM(S): Homo sapiens

PROVIDER: GSE63492 | GEO | 2016/06/30

SECONDARY ACCESSION(S): PRJNA268036

REPOSITORIES: GEO

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Revisiting the microRNA expression profiling of human intervertebral disc degeneration (IDD)

Project description:MicroRNA expression profiling of human nucleus pulposus derived from patients with IDD in comparison with those derived from cadaveric disc as normal control. We have identified the expression profiles of miRNAs in IDD using scoliotic nucleus pulposus as controls (GSE19943). It is noteworthy that scoliotic discs are not strictly normal discs. Therefore, the microRNA expression profiles were revisited using normal discs as control. Two-condition experiment: control nucleus pulposus vs. degenerative nucleus pulposus. Biological replicates: 5 control, 5 degenerated, independently harvested (the same samples as in GSE56081). Four replicates per array.

2016-06-30 | E-GEOD-63492 | biostudies-arrayexpress

The expression profiling of circular RNAs (circRNA) in human intervertebral disc degeneration (IDD)

Project description:Circular RNA expression profiling of human nucleus pulposus derived from patients with IDD in comparison with those derived from cadaveric disc as normal control. We have identified the expression profiles of miRNAs (GSE63492), lncRNAs, mRNAs (GSE56081) in IDD using 5 normal discs as control and 5 IDD discs. Accumulating evidence indicates that circRNAs are key regulators of gene expression by interacting with miRNAs. circRNA is a novel type of RNA that, unlike linear RNA, forms a covalently closed continuous loop, and is highly represented in the eukaryotic transcriptome. Two-condition experiment: control nucleus pulposus vs. degenerative nucleus pulposus. Biological replicates: 5 control, 5 degenerated, independently harvested (the same samples as GSE56081 and GSE63492). Four replicates per array.

2016-08-04 | E-GEOD-67566 | biostudies-arrayexpress

The expression profiling of circular RNAs (circRNA) in human intervertebral disc degeneration (IDD)

2016-08-04 | GSE67566 | GEO

The long noncoding RNA expression profile of human intervertebral disc degeneration identified by microarray analysis

Project description:In addition to the well-known short noncoding RNAs as miRNAs, increasing evidence suggests that long noncoding RNAs (lncRNAs) act as key regulators in a wide aspect of biologic processes. Dysregulated expression of lncRNAs has been demonstrated being implicated in a variety of human diseases. However, there is relative paucity of information regarding the role of lncRNAs in intervertebral disc degeneration (IDD) hitherto. We have addressed the expression profiles of miRNAs in IDD previously. To determine whether lncRNAs is differentially expressed in IDD, we employed a lncRNA-mRNA microarray analysis of human nucleus pulposus (five degenerative as IDD and five normal specimens as control). With abundant probes accounting for 33,045 lncRNAs and 30,215 coding transcripts in our microarray, microarray data profiling indicated that 18995 lncRNAs and 14635 mRNAs were detected in all samples with 2309 lncRNAs and 3017 mRNAs differentially expressed in degenerated samples. Amongst them, 164 lncRNAs (97 up and 67 down) and 265 mRNAs were highly differentially expressed with an absolute fold change greater than ten. The upregulated mRNAs included the extracellular matrix components as COL1A2, LUM, FN1ACAN, DCN and ITFG2. 1100 lncRNAs and 1379 mRNAs were altered in the same direction in at least 4 of the 5 degenerative samples with fold change greater than 2 respectively. Three lncRNAs were chosen for the real-time quantitative PCR (qRT-PCR) analysis. qRT-PCR results showed a high consistency with the microarray data. In this study, to explore the potential involvement of lncRNAs in IDD, we conducted lncRNA and mRNA profiling in 5 human control nucleus pulposus tissue and 5 degenerative nucleus pulposus tissue by microarray.Biological replicates: 5 control, 5 degenerated, independently harvested.

2014-11-17 | E-GEOD-56081 | biostudies-arrayexpress

HO1 activates autophagy to protect intervertebral disc degeneration

Project description:Intervertebral disc degeneration (IDD) is majorly resulted from disordered extracellular matrix (ECM) metabolism, including decreased anabolism and increased catabolism activities in the nucleus pulposus (NP) cells of discs. Pro-inflammatory cytokines such as interleukin-1β (IL-1β) are considered to be potent mediators of ECM loss. We reported previously that hemeoxygenase-1 (HO-1) inducer cobalt protoporphyrin IX (CoPP) could attenuate the ECM breakdown which induced by IL-1β, however, the underlying mechanism remains elusive. Here we found that autophagy family genes were involved in the HO-1 mediated anti-inflammatory processes in human NP cells by using high throughput RNA-Seq technique. These findings suggest that autophagy might play a role in inflammation related ECM metabolism disorder, thus offering a direction of our in-depth study and providing a framework for the searching of potential therapeutic targets in the treatment of IDD

2021-12-31 | GSE113199 | GEO

Shared and compartment-specific processes in nucleus pulposus and annulus fibrosus during intervertebral disc degeneration

Project description:Elucidating how cell populations promote onset and progression of intervertebral disc degeneration (IDD) has the potential to enable more precise therapeutic targeting of cells and mechanisms. Single cell RNA-sequencing (scRNA-seq) was performed on surgically separated annulus fibrosus (AF) (19,978; 26,983 cells) and nucleus pulposus (NP) (20,884; 24,489 cells) from healthy and diseased human intervertebral discs (IVD). In both tissue types, we observed depletion of cell subsets involved in maintenance of healthy IVD, specifically the immature cell subsets – fibroblast progenitors and stem cells – indicative of an impairment of normal tissue self-renewal. We also identified tissue-specific changes. In NP, several fibrotic populations were increased in degenerated IVD, indicating tissue-remodeling. In degenerated AF, we identified a novel disease-associated subset, which is a stem cell-derived abnormally differentiated chondrocytic population and expresses disease-promoting genes. It was associated with pathogenic biological processes and the main gene regulatory networks includedthrombospondinsignaling and FOXO1 transcription factor. Our data reveal new insights of both shared and tissue-specific changes in specific cell populations in AF and NP during IVD degeneration. These identified mechanisms and molecules are novel and more precise targets for IDD prevention and treatment.

2024-04-05 | GSE230808 | GEO

Downregulation of miR-760 Causes Human Intervertebral Disc Degeneration by Targeting the MyD88/Nuclear Factor-Kappa B Signaling Pathway

Project description:Dysregulation of microRNAs (miRNAs) plays a critical role in the development of intervertebral disc degeneration (IDD). In this study, we present evidence from in vitro and in vivo research to elucidate the mechanism underlying the role of miR-760 in IDD. miRNA microarray and quantitative reverse transcription-polymerase chain reaction were used to determine the miRNA profiles in patients with IDD. Functional analysis was performed to evaluate the role of miR-760 in the pathogenesis of IDD. Luciferase reporter and western blotting assays were used to confirm the miRNA targets. The expression of miR-760 was significantly decreased in degenerative nucleus pulposus (NP) cells and negatively correlated with disc degeneration grade. Functional assays demonstrated that miR-760 delivery significantly increased NP cell proliferation and promoted the expression of collagen II and aggrecan. Moreover, MyD88 was identified as a target gene of miR-760. miR-760 effectively suppressed MyD88 expression by interacting with the 3′-untranslated region, which was abolished by miR-760 binding site mutations. An in vivo experiment using an IDD mouse model showed that the upregulation of miR-760 could effectively suspend IDD. Therefore, miR-760 was found to play an important role in IDD and can be used as a promising therapeutic target for the treatment of patients with IDD.

2022-03-17 | E-MTAB-11554 | biostudies-arrayexpress

Therapeutic potential of targeting miR-141 in intervertebral disc degeneration: first steps toward the clinic

Project description:Understanding the molecular mechanisms regulating the maintenance and destruction of intervertebral disc may lead to the development of new therapies for intervertebral disc degeneration (IDD). Here we present evidence from miRNA microarray analyses of clinical data sets along with in vitro and in vivo experiments that miR-141 is a key regulator of IDD. Gain- and loss-of-function studies show that miR-141 drives IDD by inducing nucleus pulposus (NP) apoptosis. Furthermore, miR-141 KO in mice attenuated spontaneous and surgically induced IDD. Mechanistically, miR-141 promotes IDD development by targeting and depleting SIRT1, a negative regulator of NF-κB pathway. Therapeutically, upregulation or downregulation of miR-141 by nanoparticle delivery in IDD model aggravated or alleviated experimental IDD, respectively. Our findings reveal a novel mechanism by which miR-141, in part, promotes IDD progression by interacting with SIRT1/NF-κB pathway. Blockade of miR-141 in vivo may serve as a potential therapeutic approach in the treatment of IDD.

2018-12-11 | GSE116726 | GEO

Sox9 Deletion Causes Severe Intervertebral Disc Degeneration Characterized by Apoptosis, Matrix Remodeling, and Compartment-Specific Transcriptomic Changes

Project description:Transcriptomic analysis of nucleus pulposus (NP) and annulus fibrosus (AF) tissues from intervertebral discs of 3-month-old mice with the conditional postnatal deletion of Sox9. The transcription factor Sox9 is essential for the maintenance and health of the intervertebral disc of mice. We examined the transcriptomic profiles of nucleus pulposus and annulus fibrosus cells in control and Sox9 conditional knock-out mice using microarrays.

2023-05-19 | GSE150850 | GEO

Single-Cell RNA-Sequencing Atlas of Bovine Caudal Intervertebral Discs: Discovery of Heterogeneous Cell Populations with Distinct Roles in Homeostasis

Project description:We investigated the heterogeneous cell populations composing Bovine Intervertebral Discs (IVDs) through single cell RNA sequencing technologies. The assay sequenced over 14,000 cells composing 5 bovine discs from 3 unique bovine tails. Through both established and custom analysis pipelines, we characterize cell heterogeneity between populations of Nucleus Pulposus and Annulus Fibrosus cells. We further characterize populations of Endothelial, Muscle, Immune, and Notochord.

2021-10-07 | GSE179714 | GEO

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