Transcriptomics,Genomics

Dataset Information

31

Expression data of bone marrow and blood monocytes from patients with rheumatoid arthritis (RA) and osteoarthritis (OA)


ABSTRACT: Rheumatoid arthritis (RA) accompanies infiltration and activation of monocytes in inflamed joints. In this study we investigated dominant alterations of RA monocytes in bone marrow (BM), blood and inflamed joints. CD14+ cells from BM and blood of RA and osteoarthritis (OA) patients were profiled with Affymetrix HG U133 Plus 2.0 Arrays. Detailed functional analysis was performed with reference transcriptomes of BM precursors, monocyte blood subsets, monocyte activation and mobilization. Cytometric profiling determined monocyte subsets of CD14++CD16-, CD14++CD16+ and CD14+CD16+ cells in BM, blood and synovial fluid (SF) and ELISAs quantified the release of activation markers into SF and serum. Investigation of genes differentially expressed between RA and OA monocytes by co-expression analysis with reference transcriptomes revealed gene patterns of early myeloid precursors in RA-BM and late myeloid precursors along with reduced terminal differentiation to CD14+CD16+ monocytes in RA blood. Patterns associated with TNF/LPS stimulation were weak and more pronounced in RA blood than BM. Cytometric phenotyping of cells in BM and blood disclosed differences related to monocyte subsets and confirmed the reduced frequency of terminally differentiated CD14+CD16+ monocytes in RA blood, as suggested by transcriptome data. Monocyte activation in SF was characterized by the predominance of CD14++CD16++CD163+HLA-DR+ cells and elevated concentrations of sCD14, sCD163 and S100P. Accelerated monocytopoiesis, BM egress and migration into inflamed joints characterise increased monocyte turnover in RA. Predominant activation in the joint suggests local and primary stimulants, which may promote also adaptive immune triggering through monocytes, thus indicating their importance for diagnostic and therapeutic strategies. Overall design: Expression profiles of human peripheral blood (PB) and bone marrow (BM) monocytes from patients with RA and OA. Monocytes from RA and OA patients with long-lasting disease that were undergoing hip-replacement surgery were collected and processed for analyses. Functional interpretation of differential expression of genes were analyzed with conventional tools like Gene Ontology, Ingenuity pathway analysis as well as with the reference transcriptomes that portrayed (1) cells of myeloid lineage in bone marrow (GSE42519), (2) monocyte subsets in blood (GSE18565), (3) monocytes activated in vitro by various inflammatory stimuli (GSE38351) and (4) leukocytes (including monocytes as well) mobilized from bone marrow into blood by G-CSF administration (GSE7400).

INSTRUMENT(S): [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array

SUBMITTER: Biljana Smiljanovic  

PROVIDER: GSE100786 | GEO | 2017-07-05

SECONDARY ACCESSION(S): PRJNA393040

REPOSITORIES: GEO

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