Whole-genome expression analysis of synovial fibroblasts in rheumatoid arthritis / 中华骨科杂志

ABSTRACT

Objective To identify the crucial gene implicated in rheumatoid arthritis (RA) pathogenesis by comparing microarray-based gene expression profiles of synovial fibroblast in arthritis patients and that in control.Methods The public datasets were obtained from NCBI GEO and EBI ArrayExpress.The qualified microarray-based gene expression profiles were integrated and normalized using the method implemented in GeneSpring software.Furthermore,the differentially expressed genes (DEGs) were identified using significance analysis of microarrays (SAM) method.The online tool DAVID and STRING were applied to conduct the enrichment analysis and gene product interaction analysis respectively.Results There were two datasets that were qualified and analyzed in the present study.A total of 336 significant DEGs were identified by comparing the whole-genome gene expression profiles from synovial fibroblast of RA patients and control group.Among these DEGs,261 were significantly downregulated and 75 upregulated.About 13.6％ of the downregulated genes were associated with extracellular matrix degradation.The COL9A3 and COL4A5,indispensable component of hyaline cartilage and basement membrane respectively,were significantly downregulated,as well as genes in WNT family,including WNT2,WNT11,and WNT16.In contrast,matrix metalloproteinase 13 (MMP13) was found to be significantly upregulated in RA patients.MMP13 is a matrix metallopeptidase that degrade extracellular matrix and hyaline cartilage,and it could possibly interact with other proteins to regulate morphogenesis.Conclusion Molecular mechanisms underlying RA pathogenesis were investigated by analyzing the public datasets.A few genes that associated with extracellular matrix degradation,construction and regulation,including MMP13,WNT2,WNT11,WNT16,COL9A3 and COL4A5,could be regarded as therapeutic targets in RA treatment.