Objectives : Joint pain causes a significant morbidity in osteoarthritis (OA). The synovium as an innervated joint structure might contribute to the peripheral pain in OA. Methods : We used a hypothesis-free next generation RNA sequencing to study protein coding and small non-coding transcriptomes in knee synovial tissues of OA patients (n=10) with high and low knee pain (evaluated by visual analogue scale) followed by Gene Ontology (GO) and pathway analyses and integration of mRNAs and small RNAs data sets. Results : We showed that 33 protein-coding genes and 35 small RNAs were differentially expressed in the knee synovium of patients with high compared to low intensity knee pain, with 30 mRNAs and 14 small RNAs being upregulated and 2 mRNAs and 21 small RNAs being downregulated. Top enriched genes, such as SDIM1 and CPE encode neuronal proteins that share molecular properties with neurotrophic factor BDNF and promote neuronal survival under cellular stress, and OTOF participates in calcium-dependent synaptic exocytosis and modulation of GABAergic activity. TrkB was enriched in several gene networks, suggesting its key role in pain-related transcriptional changes in OA joint. Downregulation of PTX3 in high pain group supports an argument that inflammation and pain are independent processes in symptomatic knee OA. MiR-146a-3p and miR150 appeared as the microRNA candidates in the pathogenesis of OA-related knee pain. Conclusions : Here we uncovered the molecular complexity of pain-related transcriptome changes in the synovium of knee joints in osteoarthritis. We identified new molecular candidates in OA pain setting a firm ground for future mechanistic studies and drug discovery in OA. Overall design: RNA-seq of mRNA and small non-coding RNA of 10 patients with high and low knee pain
Pain-Associated Transcriptome Changes in Synovium of Knee Osteoarthritis Patients.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesOxidative stress is a hallmark of inflammation in infection or sterile tissue injury. We show that partially oxidized phospholipids of microvesicles (MVs) from plasma of patients with rheumatoid arthritis or cells exposed to oxidative stress induce activation of TLR4. MVs from healthy donors or reconstituted synthetic MVs can be converted to TLR4 agonists by limited oxidation, while prolonged oxidation abrogates the activity. Activation by MVs mimics the mechanism of TLR4 activation by LPS. However, LPS and MVs induce significantly different transcriptional response profile in mouse BMDMs with a strong inflammation-resolving component induced by the endogenous signals. MVs thus represent a ubiquitous endogenous danger signal released under the oxidative stress, which underlies the pervasive role of TLR4 signaling in inflammation.
Toll-like receptor 4 senses oxidative stress mediated by the oxidation of phospholipids in extracellular vesicles.
Sex
View SamplesLncRNA H19X was silienced in dermal fibroblats of systemic sclerosis patients with antisense oligonuclotides. The hypothesis tested in the present study was that H19X is an important factor in the development of TGFb-driven fibrosis. Results provide important information about the role H19X in fibroblasts in particolar on extracellular matrix production and cell cycle regulation.
Long noncoding RNA H19X is a key mediator of TGF-β-driven fibrosis.
Specimen part, Disease, Disease stage, Treatment
View SamplesAnalysis of the transcriptome of mononuclear side population (SP) and main population (MP) cells of human fetal skeletal muscle from 12 human subjects of gestational age 14-18 weeks.
Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by BMP4 and its antagonist Gremlin.
Specimen part
View SamplesFunctional analysis of ABCB5 in A375 and G3361 melanoma cells, by comparing stably-transfected controls to ABCB5-shRNA-targeted cells.
ABCB5 maintains melanoma-initiating cells through a proinflammatory cytokine signaling circuit.
Specimen part, Cell line
View SamplesThe purpose of this experiment was to identify genes responding differently to a 24 h low red to far red ratio (R:FR) treatment in plants grown at 16 and 22 degrees
Light-quality regulation of freezing tolerance in Arabidopsis thaliana.
Age
View SamplesThis experiment was a time course performed over 24 hours to look at the effects on gene expression of exposure to low red:far-red ratio light in Arabidopsis thaliana plants. In this way genes involved in the shade avoidance response might be identified. This experiment was designed for gene identification only and containes no replicates,genes identified were verified by quantitative PCR for publication.
Gating of the rapid shade-avoidance response by the circadian clock in plants.
Specimen part, Disease, Disease stage, Subject
View SamplesMelanoma growth is driven by malignant melanoma initiating cells (MMIC) identified by expression of the ATP-binding cassette (ABC) member, ABCB5. ABCB5+ melanoma subpopulations have been shown to overexpress the vasculogenic differentiation markers CD144 (VE-cadherin) and TIE-1 and are associated with CD31-negative vasculogenic mimicry (VM), an established biomarker associated with increased patient mortality. Here we identify a critical role for VEGFR-1 signaling in ABCB5+ MMIC-dependent VM and tumor growth. Global gene expression analyses, validated by mRNA and protein determinations, revealed preferential expression of VEGFR-1 on ABCB5+ tumor cells purified from clinical melanomas and established melanoma lines. In vitro, VEGF induced in a VEGFR-1-dependent manner expression of CD144 in ABCB5+ subpopulations that constitutively expressed VEGFR-1, but not in ABCB5- bulk populations that were predominantly VEGFR-1-negative. In vivo, melanomaspecific shRNA-mediated knockdown of VEGFR-1 blocked the development of ABCB5+ VM morphology and inhibited ABCB5+ VM-associated production of the secreted melanoma mitogen, laminin. Moreover, melanoma-specific VEGFR-1 knockdown markedly inhibited tumor growth (by >90%). Our results demonstrate that VEGFR-1 function in MMIC regulates VM and associated laminin production, and show that this function represents one mechanism through which MMIC promote tumor growth.
VEGFR-1 expressed by malignant melanoma-initiating cells is required for tumor growth.
Specimen part
View SamplesCD20 is a clinically validated target for Non-Hodgkins lymphomas and autoimmune diseases. Interactions of CD20 with the B cell receptor (BCR) and components of the BCR signaling cascade have been reported. In this study we show that antibodies against CD20 or activation of the BCR by specific antibodies induce very similar expression patterns of up- or down-regulated genes in NHL cell lines indicating that CD20 may play a role in BCR signaling and vice versa.
Antibodies against CD20 or B-cell receptor induce similar transcription patterns in human lymphoma cell lines.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Contribution of stress responses to antibiotic tolerance in Pseudomonas aeruginosa biofilms.
No sample metadata fields
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