Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcriptional analysis of normal and pathological synovial fibroblasts

ABSTRACT: The aim of this study was to compare gene expression between two pathological groups of human synovial fibroblasts (SF) from rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissues with normal SF from healthy individuals (HSF). We used microarray expression profiling in SF cultured from OA, RA and normal synovial tissues. We found larger numbers of transcripts with differential expression in OASF compared to the other groups than in RASF compared to HSF. This data demonstrate that cultured OASF display a more robust transcriptomic profile than RASF when compared to HSF. Synovial fibroblasts were obtained from 9 patients with rheumatoid arthritis (RASF), 11 sex and age matched adult healthy donors (HSF) and 11 sex and age matched patients with OA (OASF). SF were collected under similar subconfluent conditions 24h after serum addition. 31 microarray data were used for determine the statistical significance (p value) of the differences in gene expression.

ORGANISM(S): Homo sapiens

SUBMITTER: Manuel Del Rey

PROVIDER: E-GEOD-29746 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcriptome analysis reveals specific changes in osteoarthritis synovial fibroblasts.

Del Rey Manuel J MJ Usategui Alicia A Izquierdo Elena E Cañete Juan D JD Blanco Francisco J FJ Criado Gabriel G Pablos José L JL

Annals of the rheumatic diseases 20111021 2

<h4>Objective</h4>Changes in rheumatoid arthritis synovial fibroblast (RASF) gene expression are usually defined by a comparison to osteoarthritis synovial fibroblasts (OASFs). This study was undertaken to analyse the transcriptome of OASFs as compared to RASFs and healthy synovial fibroblasts (HSFs).<h4>Methods</h4>The authors used microarray messenger RNA expression profiling of synovial fibroblasts cultured from osteoarthritis (OA), rheumatoid arthritis and normal synovial tissues. Quantitati ...[more]

PMID: 22021863

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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

Dataset Information

Transcriptional analysis of normal and pathological synovial fibroblasts

Publications

Transcriptome analysis reveals specific changes in osteoarthritis synovial fibroblasts.

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