Identification of transcription regulatory relationships in rheumatoid arthritis and osteoarthritis

Abstract

Rheumatoid arthritis (RA) is recognized as the most crippling or disabling type of arthritis, and osteoarthritis (OA) is the most common form of arthritis. These diseases severely reduce the quality of life, and cause high socioeconomic burdens. However, the molecular mechanisms of RA and OA development remain elusive despite intensive research efforts. In this study, we aimed to identify the potential transcription regulatory relationships between transcription factors (TFs) and differentially co-expressed genes (DCGs) in RA and OA, respectively. We downloaded the gene expression profiles of RA and OA from the Gene Expression Omnibus and analyzed the gene expression using computational methods. We identified a set of 4,076 DCGs in pairwise comparisons between RA and OA patients, RA and normal donors (NDs), or OA and ND. After regulatory network construction and regulatory impact factor analysis, we found that EGR1, NFE2L1, and NFYA were crucial TFs in the regulatory network of RA and NFYA, CBFB, CREB1, YY1 and PATZ1 were crucial TFs in the regulatory network of OA. These TFs could regulate the DCGs expression to involve RA and OA by promoting or inhibiting their expression. Altogether, our work may extend our understanding of disease mechanisms and may lead to an improved diagnosis. However, further experiments are still needed to confirm these observations.

Genetic loci that regulate ectopic calcification in response to knee trauma in LG/J by SM/J advanced intercross mice

“…Interestingly, in addition to Ank , we found three other candidates ( Pon1 , Il1r2 , and Tbkbp1 ) associated with human ankylosing spondylitis, OA, and RA . Members of the IL1 gene cluster also play roles in growth plate and bone remodeling .…”

“…Playing a role in normal bone development, Nfe2l1 ( C11.1 ) contains six conserved noncoding SNPs. In humans, NFE2l1 is an important transcription factor implicated in the regulation of genes differentially expressed between normal and RA patients . Trpm3 is a calcium permeable channel associated with human RA through dysregulated synoviocyte secretion of hyaluronic acid .…”

Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation

“…The number of studies aimed at identifying disease-specific signatures in rheumatology with microarray-based methods is limited [30,31,35,56-60]. Also, very few datasets addressing this question are publicly available and have been repeatedly used for bioinformatic analyses.…”

“…This has been applied to discriminate early versus late RA [29] and to discriminate RA versus OA [30,31]. In addition, differentially expressed genes have been successfully used to predict the response of RA patients to therapeutic approaches, for example, the capability of certain (type I interferon-responsive) genes to predict rituximab nonresponders [32] and anti-tumor necrosis factor nonresponders [33] or to define homogeneous subgroups within a heterogeneous disease such as RA [22].…”

Expression Profiling and Functional Implications of a Set of Zinc Finger Proteins, ZNF423, ZNF470, ZNF521, and ZNF780B, in Primary Osteoarthritic Articular Chondrocytes

“…Taken together, the results illustrated in this paper suggest that ZNF423 underexpression may represent a useful OA-associated biomarker and possibly be a factor in OA pathogenesis. In this regard, it is interesting to notice that a recent in silico analysis of differentially coexpressed genes identified ZNF423 among the ten top-ranked transcription factors functionally relevant to OA [56]. …”