Lumbar intervertebral disc mRNA sequencing identifies the regulatory pathway in patients with disc herniation and spondylolisthesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA612336 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11298865_1.fastq.gz | Fastqsanger.gz | |||
| SRR11298865_2.fastq.gz | Fastqsanger.gz | |||
| SRR11298866_1.fastq.gz | Fastqsanger.gz | |||
| SRR11298866_2.fastq.gz | Fastqsanger.gz | |||
| SRR11298867_1.fastq.gz | Fastqsanger.gz |
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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:Herniation of the intervertebral disc (IVDH) is the most common cause of neurological and intervertebral disc degeneration-related diseases. Since the disc starts to degenerate before it can be observed by currently available diagnostic methods, there is an urgent need for novel diagnostic approaches. To identify molecular networks and pathways which may play important roles in intervertebral disc herniation, as well as to reveal the potential features which could be useful for monitoring disease progression and prognosis, multi-omics profiling including high-resolution LC-MS-based metabolomics and proteomics was performed. Furthermore, multi-omics data were integrated to decipher a complex interaction between individual omic layers leading to improved prediction model. Together with metabolic pathways related to amino acids and lipid metabolism, and coagulation cascades, our integromics prediction model identified the key features in IVDH, namely the proteins FSTL1, SCG5, NUCB1 and CRSP2 and the metabolites N-acetyl-D-glucosamine and adenine, involved in neuropathic pain, myelination, neurotransmission and inflammatory response, respectively. Their clinical application is to be further investigated. The utilization of novel integrative interdisciplinary strategy may provide opportunities to apply the innovative diagnostic and monitoring methods for degenerative spinal disorders.
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Project description:Here, we show results from next generation RNA sequencing (RNA-seq) on mRNA isolated from 10 human nucleus pulposus (NP) samples of lumbar degenerated discs (DH and DS; n=5 for each tissue) and other musculoskeletal tissues (Bone, cartilage, growth plate, and muscle; n=7 for each tissue). Pathway and network analyses based on gene ontology (GO) terms were used to identify the biological functions of differentially expressed mRNAs. A total of 701 genes were found to be significantly upregulated in lumbar NP tissue compared to other musculoskeletal tissues. These differentially expressed mRNAs were primarily involved in DNA damage, immunity and G1/S transition of mitotic cell cycle. Interestingly, DH-specific signaling genes showed major network in chemotactic (e.g., CXCL10, CXCL11, IL1RL2 and IL6) and matrix-degrading pathway (e.g., MMP16, ADAMTSL1, 5, 8, 12, and 15), while DS-specific signaling genes were found to be those involved in cell adhesion (e.g., CDH1, EPHA1and EFNA2) and inflammatory cytokines (e.g., CD19, CXCL5, CCL24, 25 and XCL2). Our findings provide new leads for therapeutic drug discovery that would permit optimization of medical or pharmacological intervention for cases of lumbar DDD.
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Project description:Human intervertebral disc tissue was obtained from patients (average age 51 yrs) undergoing surgery for lumbar interbody fusion (n=3) or lumbar disc herniation (n=1). Cells were isolated by sequential pronase-collagenase digestion [3]. Cells were passaged twice in monolayer and suspended at a density of 2 x 106 cells/ml in 1.2% alginate (low viscosity, Sigma Chemical, St Louis, MO) dissolved in 150 mM NaCl. Alginate beads were formed by dropwise addition of the alginate from a 22 gauge needle into 102 mM CaCl2, followed by 10 minutes of curing, as described previously [13, 27]. Cell-gel beads were incubated in cell culture media consisting of Ham’s F-12 medium (Gibco BRL, Grand Island, NY), supplemented with 10% FBS (HyClone, Logan, UT), 25 μg/ml ascorbic acid (Sigma, St. Louis, MO), 100 U/ml penicillin, 100 μg/ml streptomycin, and 1 μg/ml Fungizone at 5% CO2 and 37° C. After 24 h, the cell culture medium was removed via pipette and exchanged for one of three osmotically active solutions, representing iso-osmotic, hyper-osmotic and hypo-osmotic media [12, 23, 34]. The iso-osmotic solution consisted of a defined cell culture medium (Ham’s F-12 with supplements as described above; 293 mOsm/kg H2O). The hypo-osmotic solution consisted of the same cell culture media diluted with de-ionized water to a final osmolarity of 250 mOsm/kg H2O. The hyper-osmotic solution consisted of the same cell culture media supplemented with sucrose to a final osmolarity of 450 mOsm/kg H20. The osmolarity of all solution formulations was determined using a freezing-point osmometer (Advanced Laboratory Wide Range 3W2, Advanced Instrument, Needham Heights, MA) as described previously [12]. Cell-alginate beads were cultured for a 4 hour period under one of these conditions, after which the cells were released from alginate in a dissolving buffer (55 mM Na-citrate and 150 mM NaCl), lysed and stored at –80°C. Intervertebral disc (IVD) cells experience a broad range of physical stimuli under physiologic conditions, including alterations in their osmotic environment. In this study, the gene expression profile of human IVD cells was quantified with gene array technology following exposure to varying osmolarity in order to capture the biological responses for a broad set of targets. A total of 42 genes were identified in IVD cells as significantly changed following culture under hyper-osmotic conditions, while a total of 18 genes were identified as significantly changed under hypo-osmotic conditions. Gene expression patterns were verified using RT-PCR. Genes identified in this study include those related to cytoskeleton remodeling and stabilization (ephrin-B2, sarcoglycan beta, IQGAP1), as well as membrane transport (ion transporter SLC21A12, osmolyte tranporter SLC5A3, monocarboxylic acid SLC16A6, and amino acid transporter SLC7A8). An unexpected finding was the differential regulation of the gene for the neurotrophin brain-derived neurotrophic factor by hyper-osmotic stimuli that may be indicative of a physiological response of IVD cells to physical stimuli important in regulating discogenic pain. Keywords = intervertebral disc Keywords = osmotic stimuli Keywords: other
2004-08-07 | GSE1648 | GEO
Project description:Proteomics for patients with intervertebral disc degeneration
2024-04-10 | PXD051351 |
Project description:Human intervertebral disc tissue was obtained from patients (average age 51 yrs) undergoing surgery for lumbar interbody fusion (n=3) or lumbar disc herniation (n=1). Cells were isolated by sequential pronase-collagenase digestion [3]. Cells were passaged twice in monolayer and suspended at a density of 2 x 106 cells/ml in 1.2% alginate (low viscosity, Sigma Chemical, St Louis, MO) dissolved in 150 mM NaCl. Alginate beads were formed by dropwise addition of the alginate from a 22 gauge needle into 102 mM CaCl2, followed by 10 minutes of curing, as described previously [13, 27]. Cell-gel beads were incubated in cell culture media consisting of Hams F-12 medium (Gibco BRL, Grand Island, NY), supplemented with 10% FBS (HyClone, Logan, UT), 25 ug/ml ascorbic acid (Sigma, St. Louis, MO), 100 U/ml penicillin, 100 ug/ml streptomycin, and 1 ug/ml Fungizone at 5% CO2 and 37 degreeC. After 24 h, the cell culture medium was removed via pipette and exchanged for one of three osmotically active solutions, representing iso-osmotic, hyper-osmotic and hypo-osmotic media [12, 23, 34]. The iso-osmotic solution consisted of a defined cell culture medium (Hams F-12 with supplements as described above; 293 mOsm/kg H2O). The hypo-osmotic solution consisted of the same cell culture media diluted with de-ionized water to a final osmolarity of 250 mOsm/kg H2O. The hyper-osmotic solution consisted of the same cell culture media supplemented with sucrose to a final osmolarity of 450 mOsm/kg H20. The osmolarity of all solution formulations was determined using a freezing-point osmometer (Advanced Laboratory Wide Range 3W2, Advanced Instrument, Needham Heights, MA) as described previously [12]. Cell-alginate beads were cultured for a 4 hour period under one of these conditions, after which the cells were released from alginate in a dissolving buffer (55 mM Na-citrate and 150 mM NaCl), lysed and stored at -80 degreeC. Intervertebral disc (IVD) cells experience a broad range of physical stimuli under physiologic conditions, including alterations in their osmotic environment. In this study, the gene expression profile of human IVD cells was quantified with gene array technology following exposure to varying osmolarity in order to capture the biological responses for a broad set of targets. A total of 42 genes were identified in IVD cells as significantly changed following culture under hyper-osmotic conditions, while a total of 18 genes were identified as significantly changed under hypo-osmotic conditions. Gene expression patterns were verified using RT-PCR. Genes identified in this study include those related to cytoskeleton remodeling and stabilization (ephrin-B2, sarcoglycan beta, IQGAP1), as well as membrane transport (ion transporter SLC21A12, osmolyte tranporter SLC5A3, monocarboxylic acid SLC16A6, and amino acid transporter SLC7A8). An unexpected finding was the differential regulation of the gene for the neurotrophin brain-derived neurotrophic factor by hyper-osmotic stimuli that may be indicative of a physiological response of IVD cells to physical stimuli important in regulating discogenic pain.
2007-08-13 | E-GEOD-1648 | biostudies-arrayexpress
Project description:The intervertebral disc (IVD) is a joint in the spine that facilitates daily physical activity, comprising of the central nucleus pulposus (NP), surrounded by the annulus fibrosus (AF) and sandwiched between two cartilage endplates that function together as a unit. Changes to the IVD occur with aging, most drastically in the NP where it experiences dehydration and loss of cellularity, directly impacting on the integrity of the biomechanical functions of the IVD. The proteome reflects the long-term accumulation of proteins and their turnover with time, which cannot be faithfully determined by the transcriptome that reflects only immediate cellular changes. The proteome of the disc, which is predominantly extracellular matrix, may therefore more accurately reflect disc function, and could provide important information about the niche in which disc cells are embedded in and can also impact on cellular function. Unfortunately, the acquisition of young healthy IVD tissues from surgeries are scarce, and it is exceedingly rare to obtain healthy samples with spatial information. Here, we examined three young healthy cadaveric lumbar discs, corresponding to three neighboring levels (L3/4, L4/5 and L5/S1), from one individual (16M); and analysed the proteome profiles of the NP, inner AF (IAF) and outer AF (OAF), in a direction-specific (both lateral and anteroposterior) manner, to gain a reference proteome of healthy discs. We identified that the central-most regions of the disc (including NP and IAF) are similar to each other and there is expression of well characterized NP markers (including KRT8/19, CD109), as well as upregulation of cartilage and cytoskeletal-related proteins (including CHRD, CHRDL2, FRZB). Furthermore, in the PCA plot, there is clear demarcation of inner and outer AF, which was found to express small proteoglycans (BGN, DCN, FMOD, OGN, PRELP) and a unique group of the collagens (COL12A1, COL14A1, COL1A1, COL6A1/2/3) and glycoproteins including CILP, CILP2, COMP, FBN1and THBS1. We also showed that in young disc, the upper levels are more similar to each other than the lower disc levels, and that directional factors (whether the tissue was from an anteroposterior or lateral direction) play minimal roles, although we also identified four modules showing strong directional trends. Using the young proteome as a baseline reference, we then examined three aged cadaveric lumbar discs (with same disc levels as the young) from another older individual (59M) to gain further understanding of age-related changes in the disc. Employing ANOVA, PCA and DEG analyses, the aged inner disc regions (including NP and IAF) were found to have similar profiles, express fewer classical NP markers, and have reduced numbers of differentially expressed proteins (DEPs) in comparison to young disc. Overall, both inner compartments and OAF of the aged disc showed an enrichment of proteins associated with inflammation and degradation. Remarkably, we discovered that in aged disc, the IAF and OAF distinction remains strong, and that the upper lumbar disc was deviated more away from their young counterparts than the lower two levels, with minimal influence by directional differences. Importantly, we further identified an abundance of blood proteins that were highly expressed in inner disc of aged discs, which suggested that age-related changes may have originated from the central NP regions of the disc. We carried out additional validation studies by examining the transcriptome of 2 independent young and aged samples, respectively, and were able to correlate transcriptome to young and aged proteome. Unique and novel to this study, we also correlated MRI imaging of the 3 aged lumbar discs and showed that there is correlation of particular types of proteins with MRI image intensity. In all, this data shed lights on the proteomic changes underlying the ageing IVDs in a region-specific manner.
2021-01-29 | PXD017740 | Pride
Project description:Adam8Mutant vs DBA intervertebral disc injury
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