Fibronectin Fragments and Canine Disc Disease
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB37492 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR4009210_1.fastq.gz | Fastqsanger.gz | |||
| ERR4009210_2.fastq.gz | Fastqsanger.gz | |||
| ERR4009220_1.fastq.gz | Fastqsanger.gz | |||
| ERR4009220_2.fastq.gz | Fastqsanger.gz | |||
| ERR4009230_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Background: Canine intervertebral disc disease (IVDD) represents a significant clinical problem in veterinary medicine, with similarities to the human pathology. Host-derived damage-associated molecular patterns like fibronectin fragments (FnF) that develop during tissue dysfunction may be of specific relevance to IVD pathologies by inducing an inflammatory response in resident cells. Aim: This project aimed to determine the presence and pathobiological role of FnF during IVD herniation in dogs, with a focus on inflammation. Methods: Herniated nucleus pulposus (NP) material from five dogs as well as non-herniated adjacent NP material from three dogs was collected during spinal surgery required due to acute IVD herniation. The presence of different types of FnF were determined by Western blot analysis. NP cells isolated from six herniated canine IVDs were then exposed to 30 kDa FnF. NP cell inflammation and catabolism was examined by investigating the expression of IL-1β, IL-6, IL-8, and COX-2, as well as MMP-1 and MMP-3 by qPCR (all targets) and ELISA (IL-6, PGE2). Results: Amongst multiple sized FnF (30, 35, 45, and >170kDa), N-terminal fragments at a size of ~30 kDa were most consistently expressed in all five herniated IVDs. Importantly, these fragments were exclusively present in herniated, but not in non-herniated IVDs. Exposure of canine NP cells to 500 nM 30 kDa FnF caused a significant upregulation of IL-6 (62.5 ± 79.9, p = 0.032) and IL-8 (53.0 ± 75.7, p = 0.031) on the gene level, whereas IL-6 protein analysis was inconclusive. Donor-donor variation was observed in response to FnF treatment, whereby this phenomenon was most evident for COX-2, with three donors demonstrating a significant downregulation (0.67 ± 0.03, p = 0.003) and three donors showing upregulation (6.9 ± 5.5, p = 0.21). Co-treatment with Sparstolonin B, a TRL-2/TRL-4 antagonist, showed no statistical difference to FnF treatment alone in all tested target genes. Conclusion: Given the presence of the 30 kDa FnF in canine herniated IVDs and the proinflammatory effect of 30 kDa FnF on NP cells, we concluded that the accumulation of FnF may be involved in the pathogenesis of canine IVDD. These results correspond to the findings in humans with IVDD.
| S-EPMC7701143 | biostudies-literature
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
Project description:In our study, MS-based high-resolution proteomic analysis of CSF have been employed in order to gain deeper insights into changes occurring during IVDH in dogs, monitoring the pathophysiological processes at the protein and metabolite levels. The proteomics study involved canine patients classified within two groups. Healthy dogs (control group) (N=6) were mix breeds (20 kg average body weight), age 2-6 years, while the intervertebral disc herniation group (N=9) were mixed breeds (body weight 6-15 kg), age 7-12 years. In IVDH dogs, disc herniation was detected in T13/L1/L2 discs by CT. The dogs in IVDH group were paraplegic with preserved deep pain reflex and underwent a surgery procedure for decompression of the spinal cord.
2021-11-25 | PXD024921 | Pride
Project description:Proteomics for patients with intervertebral disc degeneration
2024-04-10 | PXD051351 |
Project description:Assessment of the putative differential gene expression profiles in high osmolality-treated bovine nucleus pulposus intervertebral disc cells for a short (5 h) and a long (24 h) time period. Identification of novel genes up- or down-regulated as an early or a late response to hyperosmotic stress. A 5 and 24 h-hyperosmotic treatment of nucleus pulposus cells led to transcriptional changes in >100 and 200 genes, respectively. Nucleus pulposus intervertebral disc cells were exposed to hyperosmotic stress for 5 and 24 h before RNA extraction and transcriptomics analysis. Three biological replicates were tested for each condition. Selected genes found to be differentially expressed were validated by RT-qPCR. Functional experiments were performed in order to assess the role of specific proteins encoded by genes found to be up-regulated in the osmo-reguatory response of intervertebral disc cells.
2015-06-19 | E-GEOD-59485 | 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:Baker2017 - The role of cytokines, MMPs and
fibronectin fragments osteoarthritis
This model is described in the article:
Mathematical modelling of
cytokines, MMPs and fibronectin fragments in osteoarthritic
cartilage.
Baker M, Brook BS, Owen MR.
J Math Biol 2017 Feb; :
Abstract:
Osteoarthritis (OA) is a degenerative disease which causes
pain and stiffness in joints. OA progresses through excessive
degradation of joint cartilage, eventually leading to
significant joint degeneration and loss of function. Cytokines,
a group of cell signalling proteins, present in raised
concentrations in OA joints, can be classified into
pro-inflammatory and anti-inflammatory groups. They mediate
cartilage degradation through several mechanisms, primarily the
up-regulation of matrix metalloproteinases (MMPs), a group of
collagen-degrading enzymes. In this paper we show that the
interactions of cytokines within cartilage have a crucial role
to play in OA progression and treatment. We develop a
four-variable ordinary differential equation model for the
interactions between pro- and anti-inflammatory cytokines, MMPs
and fibronectin fragments (Fn-fs), a by-product of cartilage
degradation and up-regulator of cytokines. We show that the
model has four classes of dynamic behaviour: homoeostasis,
bistable inflammation, tristable inflammation and persistent
inflammation. We show that positive and negative feedbacks
controlling cytokine production rates can determine either a
pre-disposition to OA or initiation of OA. Further, we show
that manipulation of cytokine, MMP and Fn-fs levels can be used
to treat OA, but we suggest that multiple treatment targets may
be essential to halt or slow disease progression.
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2024-09-02 | BIOMD0000000928 | BioModels
Project description:Although it is well-recognized that apoptosis, senescence, and increased production of inflammatory cytokines and catabolic products are important factors in the degeneration of the human intervertebral disc, there is poor understanding of the underlying cause. The objective of the present study was to analyze gene expression patterns in the human annulus disc tissue.
2011-03-01 | GSE23130 | GEO
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
Project description:The intervertebral disc is a specialized fibrocartilage structure of the spinal column that is pivotal for spinal mobility and function. It is composed of 3 distinct anatomical components: the annulus fibrosus, nulceus pulposus and cartilage endplates. We used 10x single cell seq to identify the various cell components of the disc as well as discover novel cell populations and signaling networks.
2024-01-26 | GSE254014 | GEO