The main pathological manifestations of rheumatoid arthritis are synovitis and bone destruction in the peripheral joints. The synovium is the inner layer of the joint capsule and consists of loose connective tissue. The normal synovium has only 2 layers, a cellular layer and a vascular layer, usually 1-3 cellular layers, so the synovium cannot be observed on imaging under normal circumstances and can only be observed when the synovium is hyperplastic. When synovial hyperplasia occurs, the synovial membrane thickens tens of times and the patient experiences swelling of the joint. The increased blood flow signal can be observed on ultrasound, which is used to determine inflammation. Why do normal synovial cells proliferate abnormally and destroy joint bones? It has been suggested that activation of fibroblast-like synovial cells (RASFs) is caused by genomic hypermethylation in rheumatoid arthritis. The genome is the sum of all DNA molecules that humans possess. Methylation is the addition of a chemical structure to some genetic segments in order to inhibit the replication of certain genes. Hypomethylation may lead to abnormal gene replication, which can lead to the synthesis of abnormal cellular components, resulting in abnormal cellular function. DNA hypermethylation was first identified in tumors and gradually found to be present in autoimmune diseases, which may be associated with an increased chance of secondary tumors in patients with autoimmune diseases. It was concluded that compared to osteoarthritic fibroblastic synoviocytes (OASFs), rheumatoid arthritis synoviocytes had fewer 5-methylcytosine and methylated CG sites upstream of the L1 open reading frame (the part of DNA that encodes proteins), both in the synovial in situ assay and after in vitro culture, and that rheumatoid arthritis synoviocytes in the proliferative state lacked a protein called Dnmt1 protein expression. Cells cultured in vitro by sequential stimulation with 5-azaC, normal fibroblast-like synoviocytes also exhibited abnormal rheumatoid arthritic synoviocytes, with a consequent upregulation of 186 genes expression more than 2-fold and increased protein levels, including growth factors and their receptors, extracellular matrix proteins, adhesion molecules, and matrix degrading enzymes. DNA hypomethylation is involved in the pathogenesis and disease progression of RA, providing new ideas for the development of new treatments for RA.