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Loss of function mutation in progressive ankylosis (Ank) gene causes aberrant mineralization and acquisition of osteoblast-like-phenotype by annulus fibrosus cells in the intervertebral disc

ABSTRACT: Transcriptomic analysis of nucleus pulposus (NP) and annulus fibrosus (AF) tissues from intervertebral discs of 3-month-old mice with loss of function mutation of Ank gene. Regulator of extracellular inorganic pyrophosphate, Ank is essential for preventing ectopic mineralization in the extracellular matrices, maintaining the health of the intervertebral disc of mice. We examined the transcriptomic profiles of nucleus pulposus and annulus fibrosus cells in control and Ank mutant mice using microarrays.

ORGANISM(S): Mus musculus

PROVIDER: GSE206997 | GEO | 2023/06/01

REPOSITORIES: GEO

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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

Transcription profiling of bovine nucleus pulposus, carticular cartilage and annulus fibrosus cells to further determine expression in normal and degenerate human intervertebral disc

Project description:The aim of this transcription profiling study was to identify novel genes that could be used to distinguish bovine Nucleus pulposus (NP) cells from articular cartilage (AC) and annulus fibrosus (AF) cells and to further determine their expression in normal and degenerate human intervertebral disc (IVD). This study has identified a number of novel genes that characterise the bovine and human NP and IVD cell phenotypes and allows for discrimination between AC, AF and NP cells.<br><br>

2010-03-05 | E-MEXP-2291 | biostudies-arrayexpress

Gene Expression Profiling Identifies Interferon Signalling Molecules and IGFBP3 in Human Degenerative Annulus Fibrosus

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

The STING pathway does not contribute to the onset of cell senescence and SASP induction in the intervertebral disc

Project description:Transcriptional analysis of 6-month-old primary nucleus pulposus (NP) and annulus fibrosus (AF) mouse disc tissues from wild-type (WT) and N153S mice, which harbor a mutation wich constiuitively activates Sting. Mouse details available here: https://www.jax.org/strain/033543 The cGAS-STING pathway promotes the senescence-associated secretory phenotype (SASP), which is associated with intervertebral disc degeneration, and has had implications in inflammatory musculoskeletal disorders. We examined the role of STING in the disc by examining the transcriptomic profiles of nucleus pulposus and annulus fibrosus cells in WT and N153S mice using microarray.

2022-07-06 | GSE188909 | GEO

TonEBP-deficiency accelerates age-dependent intervertebral disc degeneration underscored by matrix remodeling, cytoskeletal rearrangements, and changes in proinflammatory gene expression

Project description:Our studies show that TonEBP-deficiency causes pronounced degeneration of all three intervertebral disc compartments with greater incidence of herniation in the mouse. The disc phenotype is marked by extracellular matrix remodeling, actin cytoskeleton rearrangements, and suppressed proinflammatory gene expression, advancing our understanding of the contributions of TonEBP in intervertebral disc homeostasis and disease. We used microarray to explore the transcriptomics of differentially expressed genes of annulus fibrosus (AF) and nucleus pulposus (NP) tissue in TonEBP haploinsufficient mice on a C57BL/6 background.

2021-08-05 | GSE135270 | GEO

Detection of CA12 as a novel NP cell surface marker

Project description:Sixteen samples; 6 nucleus pulposus, 6 annulus fibrosus and 4 articular cartilage were compared to find transcriptional differences.

2010-12-27 | E-MEXP-2936 | biostudies-arrayexpress

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

An Organ Culture System to Model Early Degenerative Changes of the Intervertebral Disc: II Profiling Global Gene Expression Changes

Project description:To mimic a degenerative insult, rat intervertebral discs were cultured in the presence of TNF-alpha, IL-1beta and serum limiting conditions. Gene expression analysis was performed using a microarray to identify differential gene expression between experimental and control groups. The discs were collected and the annulus fibrosus (AF) was separated from the nucleus pulposus (NP). Total RNA from NP was used for RNA extraction and hybridization on Affymetrix microarrays: Control group - Ctr-1, Ctr-2, Ctr-3, Ctr-4 and Experimental group-Exp-1, Exp-2, Exp-3, Exp-4.

2012-11-29 | E-GEOD-42611 | biostudies-arrayexpress

Abcc6 null mice a model mineralization disorder PXE show vertebral osteopenia without enhanced intervertebral disc calcification with aging

Project description:Transcriptomic analysis of annulus fibrosus (AF) tissues from intervertebral discs of 7-month-old mice with the global deletion of ABCC6. ABCC6 is an efflux transporter of ATP in hepatic cells and loss of function results in metabolic ectopic mineralization disorder pseudoxanthoma elsaticum. To understand the role of ABCC6 and ectopic mineralization in the disc, we examined the transcriptomic profiles of annulus fibrosus cells in control and ABCC6 knock-out mice using microarrays.

2021-11-17 | GSE188943 | 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

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