Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of synovial tissue mRNA from 21 rheumatoid arthritis patients and 9 osteoarthritis patients vs a common reference sample on lymphochips

ABSTRACT: Synovial tissue mRNA from 21 RA patients and 9 OA patients is hybridized against a common reference sample on lymphochips.

ORGANISM(S): Homo sapiens

SUBMITTER: Janos Demeter

PROVIDER: E-SMDB-2032 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activation of the STAT-1 pathway between rheumatoid tissues.

van der Pouw Kraan Tineke C T M TC van Gaalen Floris A FA Kasperkovitz Pia V PV Verbeet Nicolette L NL Smeets Tom J M TJ Kraan Maarten C MC Fero Mike M Tak Paul-Peter PP Huizinga Tom W J TW Pieterman Elsbet E Breedveld Ferdinand C FC Alizadeh Ash A AA Verweij Cornelis L CL

Arthritis and rheumatism 20030801 8

<h4>Objective</h4>To generate a molecular description of synovial tissue from rheumatoid arthritis (RA) patients that would allow us to unravel novel aspects of pathogenesis and to identify different forms of disease.<h4>Methods</h4>We applied complementary DNA microarray analysis to profile gene expression, with a focus on immune-related genes, in affected joint tissues from RA patients and in tissues from osteoarthritis (OA) patients as a control. To validate microarray data, real-time polymer ...[more]

PMID: 12905466

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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

Transcription profiling of synovial tissue mRNA from 21 rheumatoid arthritis patients and 9 osteoarthritis patients vs a common reference sample on lymphochips

Publications

Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activation of the STAT-1 pathway between rheumatoid tissues.

Similar Datasets

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