MiRNA expression in RA and OA human fibroblast-like synoviocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: philippe georgel
PROVIDER: E-GEOD-72564 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Homo sapiens microRNAs (miRNAs) are invovolved in the regulation of multiple cellular processes and have been linked to many conditions in humans, including rheumatic diseases such as rheumatoid arthritis (RA). Here, we used high throughput expression analysis to assess the overall miRNA expression level in FLS isolated from RA patients in comparison with miRNA expressed in FLS from osteoarthritic (OA) patients.
2015-09-01 | GSE72564 | GEO
Project description:In osteoarthritis (OA) and rheumatoid arthritis (RA), many pathological alterations result from aberrant macrophage hyperactivation in the inflamed synovial membrane, and inhibition of macrophage effector functions is a therapeutic strategy in both diseases. Little is known, about the specific genetic circuits that are differentially deregulated in RA and OA macrophages. microRNA (miR) are short single stranded non-coding RNAs involved in the post-transcriptional regulation of gene expression. Altered expression of miRs has been described under various pathological conditions, including rheumatic and other autoimmune diseases. Here we compared the miR expression profile in macrophages isolated from OA and RA patients miR expression in OA and RA macrophages was analyzed using Exiqon miRCURY microarrays. Three biological replicates (patients) were analyzed. Two samples (RA vs OA) were hybridized per microarray.
2016-02-05 | E-GEOD-63745 | biostudies-arrayexpress
Project description:Fibroblast-like synoviocyte (FLS) constitutes a major cell subset of rheumatoid arthritis (RA) joint. Dysregulation of microRNAs (miRNAs) contributes to FLS activation in the context of chronic inflammation. However, functional association of the miRNAs-targets relationships characterizing FLS phenotypes in RA has not been fully elucidated yet. Thus, we uncovered the novel miRNA-target interactions characterizing pathologic phenotypes of RA-FLS. We performed microarray analyses of miRNA in RA- and osteoarthritis (OA) FLS with or without interleukin-1β (IL-1β) stimulation. The miRNA-target prediction and network model-ing were performed using TargetScan and Cytoscape. Identified miRNA-target relationships and their cellular functions were validated in vitro.
2017-10-31 | GSE91026 | GEO
Project description:Rheumatoid synoviocytes, which consist of fibroblast-like synoviocytes (FLS) and synovial macrophages (SM), are crucial for the progression of rheumatoid arthritis (RA). Particularly, FLS of RA patients (RA-FLS) exhibit invasive characteristics reminiscent of cancer cells, destroying cartilage and bone, although it remains unresolved how RA-FLS exhibit invasive phenotype. RA-FLS and SM originate differently from mesenchymal and myeloid cells, respectively, but share many pathologic functions. However, the molecular signatures and biological networks representing the distinct and shared features of the two cell types are unknown. Presently, we performed global transcriptome profiling of FLS and SM obtained from RA and osteoarthritis patients. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining invasiveness of RA-FLS and pro-inflammatory properties of RA synovial macrophages (RA-SM), respectively. Interestingly, under interleukin1β-stimulated condition, RA-FLS newly acquired pro-inflammatory signature mimicking RA-SM without losing invasive properties. We next reconstructed a network model that delineates the shared, RA-FLS-dominant (invasive), and RA-SM-dominant (inflammatory) processes. From the network model, we selected 13 genes, including POSTN and TWIST1, as novel regulator candidates responsible for FLS invasiveness. Of note, POSTN and TWIST1 expressions were elevated in independent RA-FLS and were further instigated by interleukin1β. In vitro functional assays demonstrated the requirement of POSTN and TWIST1 for migration and invasion of RA-FLS stimulated with interleukin1β. Taken together, our systems approach to rheumatoid synovitis provides a basis for identifying novel regulators responsible for pathological features of RA-FLS and RA-SM, demonstrating how a certain type of cells acquires functional redundancy under chronic inflammatory conditions. To identify molecular signatures of FLS and MLS in RA joints, we isolated FLS from synovial tissues of RA and osteoarthritis (OA) patients, obtained synovial macrophages from synovial fluid of RA patients, and differentiated control macrophages from peripheral blood of healthy subjects. Also, we stimulated FLS with IL1β, and then analyzed gene expression profiles of both IL1β-stimulated RA-FLS and OA-FLS
2014-01-09 | E-GEOD-49604 | biostudies-arrayexpress
Project description:Gene expression profiling of BMMC from patients with rheumatoid arthritis (RA) vs. osteoarthritis (OA). Bone marrow was obtained from patients with RA (n=9) or OA (n=10). The bone marrow samples from the 10 OA patients are used as controls.
2011-05-31 | E-GEOD-27390 | biostudies-arrayexpress
Project description:The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins on a global level in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without knee OA. Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e. interplay) between the proteins in each group. More proteins were increased in early-OA vs controls than late-stage OA vs controls. For most of these proteins, the fold changes between late-stage OA vs controls and early stage OA vs controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time this study illustrated distinct patterns in protein co-expression suggesting that the global interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should probably focus on earlier stages of the disease than previously considered.
2022-01-27 | PXD023708 | Pride
Project description:Objectives: Epigenetics can influence disease susceptibility and severity. While DNA methylation of individual genes has been explored in autoimmunity, no unbiased systematic analyses have been reported. Therefore, a genome-wide evaluation of DNA methylation loci in fibroblast-like synoviocytes (FLS) isolated from the site of disease in rheumatoid arthritis (RA) was performed. Methods: Genomic DNA was isolated from six RA and five osteoarthritis (OA) FLS lines and evaluated using the Illumina HumanMethylation450 chip. Cluster analysis of data was performed and corrected using Benjamini–Hochberg adjustment for multiple comparisons. Methylation was confirmed by pyrosequencing and gene expression was determined by qPCR. Pathway analysis was performed using the Kyoto Encyclopedia of Genes and Genomes. Results: RA and control FLS segregated based on DNA methylation, with 1859 differentially methylated loci. Hypomethylated loci were identified in key genes relevant to RA, such as CHI3L1, CASP1, STAT3, MAP3K5, MEFV and WISP3. Hypermethylation was also observed, including TGFBR2 and FOXO1. Hypomethylation of individual genes was associated with increased gene expression. Grouped analysis identified 207 hypermethylated or hypomethylated genes with multiple differentially methylated loci, including COL1A1, MEFV and TNF. Hypomethylation was increased in multiple pathways related to cell migration, including focal adhesion, cell adhesion, transendothelial migration and extracellular matrix interactions. Confirmatory studies with OA and normal FLS also demonstrated segregation of RA from control FLS based on methylation pattern. Conclusions: Differentially methylated genes could alter FLS gene expression and contribute to the pathogenesis of RA. DNA methylation of critical genes suggests that RA FLS are imprinted and implicate epigenetic contributions to inflammatory arthritis. Fibroblast-like synoviocyte cell-lines from osteoarthritis (OA) and rheumatoid arthritis (RA) patients.
2013-04-25 | E-GEOD-46364 | biostudies-arrayexpress
Project description:All the synovial tissue specimens for TMT relative quantitative proteomics and further experiments were obtained from the patients with RA or OA undergoing surgical joint replacement at the clinical of joint surgery (Xi'an Hong Hui Hospital, Xi'an Jiaotong University, China). The diagnosis of the patients were accorded to the criteria of the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) in 2010.a quantitative proteomic profiling of synovial tissue obtained from RA and OA patients was carried out by using TMT labeling followed by high resolution mass spectrometry analysis. We have identified 4822 proteins out of which 510 proteins were found to be differentially expressed by ≥1.2 fold change in the synovial tissue from RA verses OA patients.
2021-12-30 | PXD027703 | Pride
Project description:Objectives: TNF-induced activation of fibroblast-like synoviocytes (FLS) is a critical determinant for synovial inflammation and joint destruction in rheumatoid arthritis (RA). The detrimental role of TNF-receptor 1 (TNFR1) has thoroughly been characterized. The contributions of TNFR2, however, are largely unknown. This study was performed to delineate the role of TNFR2 in human FLS activation. Methods: TNFR2 expression in synovial tissue samples was determined by immunohistochemistry. Expression of TNFR2 was silenced using RNAi or CRISPR/Cas9 technologies. Global transcriptional changes were determined by RNA-seq. QPCR, ELISA and immunoblotting were used to validate RNA-seq results and to uncover pathways operating downstream of TNFR2 in FLS. Results. TNFR2 expression was increased in RA when compared to OA synovial tissues. In particular, RA-FLS demonstrated higher levels of TNFR2 when compared to OA-FLS. TNFR2 expression in RA-FLS correlated with RA disease activity, synovial T- and B-cell infiltration. TNF and IL1 were identified as inflammatory mediators that upregulate TNFR2 in RA-FLS. Silencing of TNFR2 in RA-FLS markedly diminished the TNF-induced expression of inflammatory cytokines and chemokines, including CXCR3-binding chemokines and the B-cell activating factor TNFSF13B. Immunobiochemical analyses revealed that TNFR2-mediated expression of inflammatory mediators critically depends on STAT1. Conclusion: Our results define a critical role for TNFR2 in FLS-driven inflammation and unfold its participation in the unresolved course of synovial inflammation in RA.
2022-04-26 | GSE195557 | GEO
Project description:Invasive pannus, mainly composed of fibroblast-like synoviocytes (FLSs), is a hallmark of rheumatoid arthritis (RA) pathology. Secreted proteins from RA-FLS play key roles in RA invasive pannus. However, RA-FLS-derived secretome associated with invasive pannus has not been systematically investigated. Here, we first identified 843 secreted proteins from RA-FLSs treated with TNFα and IL-1β using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Functional enrichment analysis revealed that 58.5% (493 proteins) of the secretome were associated with pannus-driven RA pathologies. Among them, parallel reaction monitoring (PRM) analysis then identified 16 secreted proteins that were increased in RA SFs (117 samples) than in OA SFs (45 samples). Of them, MYH9 further showed significant positive correlations with RA pathological parameters, such as synovial hyperplasia, increased articular vascularity, and inflammation severity. Molecular and cellular experiments confirmed that MYH9 was expressed in RA-FLSs and more highly under disease-aggravating conditions, and MYH9 depletion significantly defected migration and invasion of RA-FLS in RA pannus. Our study provides a comprehensive resource of RA-FLS-derived secretome, and our results suggest MYH9 that was increased in RA SF and strongly correlated with disease severity as a potential therapeutic target for invasive pannus.
2023-06-30 | PXD041077 | Pride