Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human synovial macrophages from rheumatoid arthritis patients

ABSTRACT: Macrophages from RA synovial fluids were compared to primary human blood-derived macrophages. Experiment Overall Design: Macrophages from synovial fluids of five RA patients were isolated by ficoll density gradient centrifugation, followed by positive selection of CD14+ cells using magnetic beads. The patientsâ?? diagnoses were determined by their physicians, in each case a Board-certified rheumatologist at the Hospital for Special Surgery, and were definite RA according to American College of Rheumatology criteria. De-identified samples were processed in an anonymous manner using a protocol approved by the Institutional Review Board of the Hospital for Special Surgery. Experiment Overall Design: Human peripheral blood mononuclear cells were isolated from venous blood of independent healthy donors by centrifugation on a Ficoll density gradient. Monocytes were obtained from PBMCs using anti-CD14 magnetic beads, and were >96% pure as verified by flow cytometry. Monocytes were differentiated into macrophages by culturing in RPMI 1640 medium supplemented with 10% fetal bovine serum and M-CSF (20 ng/ml). The viability and purity of macrophages was comparable in all conditions Experiment Overall Design: Gene expression was analyzed using Affymetrix microarrays and protocols.

ORGANISM(S): Homo sapiens

SUBMITTER: Taras Antoniv

PROVIDER: E-GEOD-10500 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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

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Transcription profiling of human synovial macrophages from rheumatoid arthritis patients

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