Functional Annotation of Rheumatoid Arthritis and Osteoarthritis Associated Genes by Integrative Genome-Wide Gene Expression Profiling Analysis

Abstract

BackgroundRheumatoid arthritis (RA) and osteoarthritis (OA) are two major types of joint diseases that share multiple common symptoms. However, their pathological mechanism remains largely unknown. The aim of our study is to identify RA and OA related-genes and gain an insight into the underlying genetic basis of these diseases.MethodsWe collected 11 whole genome-wide expression profiling datasets from RA and OA cohorts and performed a meta-analysis to comprehensively investigate their expression signatures. This method can avoid some pitfalls of single dataset analyses.Results and ConclusionWe found that several biological pathways (i.e., the immunity, inflammation and apoptosis related pathways) are commonly involved in the development of both RA and OA. Whereas several other pathways (i.e., vasopressin-related pathway, regulation of autophagy, endocytosis, calcium transport and endoplasmic reticulum stress related pathways) present significant difference between RA and OA. This study provides novel insights into the molecular mechanisms underlying this disease, thereby aiding the diagnosis and treatment of the disease.

Osteoarthritis: toward a comprehensive understanding of pathological mechanism

“…81–85 Indeed, the recent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of OA and control samples provide evidence that inflammation signals contribute to OA pathogenesis through cytokine-induced mitogen-activated protein (MAP) kinases, NF-κB activation, and oxidative phosphorylation. 86 …”

Inflammation and epigenetic regulation in osteoarthritis

“…Elevated systemic inflammation was also observed in obesity mice with DMM surgery, including cytokine and chemokine production, synovial tissue expansion, inflammatory cell infiltration, and NF-κB pathway activation (59), suggesting obesity plays a role during PTOA development. Indeed, recent transcriptomic analyses provide evidence that inflammatory signals contribute to OA pathogenesis through cytokine-induced MAP kinases, NF-κB activation, and oxidative phosphorylation (60). …”

“…As a result, NF-κB function impacts multiple cellular outcomes, including cell migration, proliferation, differentiation, and survival (77). While controlled NF-κB-mediated responses promote homeostasis, persistently elevated responses of this pathway are associated with diseases such as rheumatoid arthritis (RA) and OA (60,78). Despite the large body of evidence on the role of TAK1-IKK2-NF-κB axis in these diseases, the mechanisms by which pathologic activity of NF-κB induces joint catabolism are largely unknown.…”

Association between the autophagy-related geneULK1and ankylosing spondylitis susceptibility in the Chinese Han population: a case–control study

“…The activation of the ULK1 complex requires the initiation of autophagy, which has been shown to be the most upstream step of autophagosome formation. Previous studies have reported that autophagy and its anti-inflammatory function contribute to both inflammatory and autoimmune diseases, such as systemic lupus erythematosus,27 rheumatoid arthritis and osteoarthritis 28. In these disease processes, autophagy could affect the selection of thymic T cell, antigen processing, cross presentation, cell survival and cytokine responses of immune cells 29.…”