Epigenetic analysis in rheumatoid arthritis synoviocytes

et al. 2019

Int. J. Med. Sci.

Synovitis in osteoarthritis (OA) the consequence of low grade inflammatory process caused by cartilage breakdown products that stimulated the production of pro-inflammatory mediators by fibroblast-like synoviocytes (FLS). FLS participate in joint homeostasis and low grade inflammation in the joint microenvironment triggers FLS transformation. In the current study, we aimed to identify differentially expressed genes and potential miRNA regulations in human OA FLS through deep sequencing and bioinformatics approaches. The 245 differentially expressed genes in OA FLS were identified, and pathway analysis using various bioinformatics databases indicated their enrichment in functions related to altered extracellular matrix organization, cell adhesion and cellular movement. Moreover, among the 14 dysregulated genes with potential miRNA regulations identified, src kinase associated phosphoprotein 2 (SKAP2), adaptor related protein complex 1 sigma 2 subunit (AP1S2), PHD finger protein 21A (PHF21A), lipoma preferred partner (LPP), and transcription factor AP-2 alpha (TFAP2A) showed similar expression patterns in OA FLS and OA synovial tissue datasets in Gene Expression Omnibus database. Ingenuity Pathway Analysis identified the dysregulated LPP participated in cell migration and cell spreading of OA FLS, which was potentially regulated by miR-141-3p. The current findings suggested new perspectives into understanding the novel molecular signatures of FLS involved in the pathogenesis of OA, which may be potential therapeutic targets.

Section: Discussionmentioning

confidence: 98%

Identification of Novel Genes in Osteoarthritic Fibroblast-Like Synoviocytes Using Next-Generation Sequencing and Bioinformatics Approaches

Chen

et al. 2019

Int. J. Med. Sci.

“…For example, compared with osteoarthritis (OA), 523 low-methylated regions are specific to RA. The regions overlap with specific motifs of transcription factors, such as GLI1, RUNX2 , and TFAP2A/C , which promote the proliferation of synovial cells and the development and migration of plasmacytoid dendritic cells in RA ( Ham et al, 2019 ). In contrast with OA, in which C18orf45, LMO4, MAP3K5, ODZ4, PKNOX2, SEPT11, MSRA , and MIR155HG are hypomethylated, PRDM16 is hypermethylated in RA ( Glossop et al, 2015 ).…”

Section: Genome-wide Methylation Profiling To Identify Ra-associated mentioning

confidence: 99%

Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis

Guo

et al. 2020

Front. Genet.

Rheumatoid arthritis (RA) is a complex disease triggered by the interaction between genetics and the environment, especially through the shared epitope (SE) and cell surface calreticulin (CSC) theory. However, the available evidence shows that genetic diversity and environmental exposure cannot explain all the clinical characteristics and heterogeneity of RA. In contrast, recent studies demonstrate that epigenetics play important roles in the pathogenesis of RA, especially DNA methylation and histone modification. DNA methylation and histone methylation are involved in innate and adaptive immune cell differentiation and migration, proliferation, apoptosis, and mesenchymal characteristics of fibroblast-like synoviocytes (FLS). Epigenetic-mediated regulation of immune-related genes and inflammation pathways explains the dynamic expression network of RA. In this review, we summarize the comprehensive evidence to show that methylation of DNA and histones is significantly involved in the pathogenesis of RA and could be applied as a promising biomarker in the disease progression and drug-response prediction. We also explain the advantages and challenges of the current epigenetics research in RA. In summary, epigenetic modules provide a possible interface through which genetic and environmental risk factors connect to contribute to the susceptibility and pathogenesis of RA. Additionally, epigenetic regulators provide promising drug targets to develop novel therapeutic drugs for RA. Finally, DNA methylation and histone modifications could be important features for providing a better RA subtype identification to accelerate personalized treatment and precision medicine.

“…Abnormal methylation regions maybe overlapped with transcription factors binding sites (TFBS) to activate enhance regulation activities. For example, RA related hypomethylated regions are found overlap with binding motifs of transcription factors such as GLI1, RUNX2, and TFAP2A/C, and these TFs are closely related to the TGF-β pathway (Ham et al, 2019). The hypermethylation genes CCR6, CMTM5, IL10RA, IL21R and IL32 in systemic lupus erythematosus and pSS while hypomethylation in RA (Wang et al, 2018).…”

Section: Genome-wide Methylation Profiling To Identify Rheumatoid Artmentioning

confidence: 99%

Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis

Guo

et al. 2020

Preprint

Rheumatoid arthritis (RA) as a complex disease is thought triggered by interaction between genetics and environment, especially the shared epitope (SE) and cell surface calreticulin (CSC) theory. However, all the evidence shows genetic diversity and environment exposure cannot explain all the clinical characteristics heterogeneity of rheumatoid arthritis. In contrast, recent studies demonstrate that epigenetics play important roles in the pathogenesis of rheumatoid arthritis, especially DNA methylation and histone modification. DNA methylation and histone methylation are involved in innate and adoptive immune cell differentiation and the migration, proliferation, apoptosis, and mesenchymal characteristics of fibroblast-like synoviocytes (FLS). Epigenetic mediated regulation to immune genes and inflammation pathway provides well explanation to dynamic expression network of rheumatoid arthritis. In this review, we summarized the comprehensive evidence to show methylation modification occurred in DNA and histone are significantly involved in the pathogenesis of rheumatoid arthritis and could be applied as the promising biomarker in the disease activity and drug response prediction. We also explained the opportunity and challenge of the current epigenetics research in rheumatoid arthritis. In summary, epigenetic modules provide possible interface through which genetic and environmental risk factors connect together to contribute to the susceptibility and pathogenesis of RA. Meanwhile epigenetic regulators provided promising drug targets to develop novel therapeutic drugs for rheumatoid arthritis. Finally, DNA methylation and histone modification will be important features to provide better rheumatoid arthritis subtype identification to accelerate personalized treatment and precision medicine.