OBJECTIVE: To examine the mechanism for the inhibited differentiation of osteoclasts in rheumatoid arthritis synovial CD14+ osteoclast precursors, the different expressions of the osteoclastogenesis-related genes in rheumatoid arthritis (RA) synovial fluid CD14+ osteoclast precursors were compared with those of normal peripheral blood (PB) CD14+ osteoclast precursors. METHODS: The expression of osteoclastogenesis-related genes were examined using a gene expression oligonucleotide microarray. To validate the results of the microarray analysis, the mRNA expressions of osteoclastogenesis-related genes were measured by real-time PCR. RESULTS: Comparative analysis of the mRNA profiles showed significantly different expression of osteoclastogenesis- related genes, such as MafB, Id3 and LILRB4, in the RA synovial CD14+ osteoclast precursors, compared to that of normal PB CD14+ osteoclast precursors. CONCLUSION: The expression of the osteoclastogenesis-related genes in RA synovial CD14+ osteoclast precursors is different from that of the normal PB CD14+ osteoclast precursors. These results suggest that the different expression of osteoclastogenesis-related genes might be involved in the altered osteoclastogenesis in RA synovial osteoclast precursors.
Arthritis, Rheumatoid ; Genes, vif ; Macrophages ; Microarray Analysis ; Oligonucleotide Array Sequence Analysis ; Osteoclasts ; RNA, Messenger ; Synovial Fluid

OBJECTIVE: We wanted to investigate the mechanisms that could account for the pathogenesis of rheumatoid arthritis, so we examined the different expressions of the genes in rheumatoid arthritis (RA) synovial fluid macrophages as compared with that of normal peripheral blood (PB) monocyte-derived macrophages using microarray and bioinformatic analysis. METHODS: We examined the expression of genes by using a gene expression oligonucleotide microarray. The differences of the gene expressions between the RA synovial macrophages and the normal PB monocytes-derived macrophages were analyzed using bioinformatic tools, including cytoscape and its plugin. RESULTS: In this study, we found that 899 genes (464 genes up-regulated and 435 genes down-regulated) were differentially expressed between the two groups. Among the 899 genes, 552 genes were included for gene ontology analysis and network analysis. Based on biological process ontology, they were categorised mainly into immune response processes, responses to stimulus and signaling and regulation of biological processes. In addition to the genes related with STAT1 and AP-1 signaling, we found that the genes involved in the antigen processing and the cell cycle are abundantly expressed in RA synovial macrophages, suggesting that these genes may play an important role in the pathogenesis of RA. CONCLUSION: Our study suggest that this approach using integration of the gene expression profile with the protein interaction data may help to find several important pathogenic mechanisms in RA.
Antigen Presentation ; Arthritis, Rheumatoid ; Biological Processes ; Cell Cycle ; Computational Biology ; Gene Expression ; Genes, vif ; Macrophages ; Oligonucleotide Array Sequence Analysis ; Synovial Fluid ; Transcription Factor AP-1 ; Transcriptome

OBJECTIVE: MicroRNAs (miRNAs) play important roles in many biological processes and recent studies have provided growing evidences that miRNA dysregulation might play important roles in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate the contribution of miRNAs to altered gene expressions in RA. METHODS: To investigate whether the differential expression of miRNA in RA could account for the altered expression of certain genes, we compared the different expressions of miRNAs and mRNAs in rheumatoid synovial fluid monocytes with that of normal peripheral blood (PB) monocytes by using a gene expression oligonucleotide microarray and a microRNA microarray. RESULTS: Comparative analysis of the mRNA profiles showed significant different expressions of 430 genes in RA synovial monocytes, of which 303 (70%) were upregulated and 127 (30%) were downregulated, as compared with that of normal PB monocytes. Out of differentially expressed 13 miRNAs, 9 miRNAs were upregulated and 4 miRNAs were downregulated in the RA synovial monocytes. A total of 62 genes were predicted as target genes of the 13 differentially expressed miRNAs in the RA synovial monocytes. Among the 62 miRNA-targeted genes, a few genes such as GSTM1, VIPR1, PADI4, CDA, IL21R, CCL5, IL7R, STAT4, HTRA1 and IL18BP have been reported to be associated with RA. CONCLUSION: In the present study, we observed that several miRNAs are differentially expressed in RA synovial monocytes, and we suggest that these different expressions of miRNAs may regulate the expression of several genes associated with the pathogenesis of RA.
Arthritis, Rheumatoid ; Biological Processes ; Gene Expression ; Genes, vif ; MicroRNAs ; Monocytes ; Oligonucleotide Array Sequence Analysis ; Receptors, Interleukin-21 ; RNA, Messenger ; Synovial Fluid