Nakano et al. demonstrated that FLS from RA patients exhibited a global DNA hypomethylation associated with an increase expression of genes related to extracellular matrix proteins, matrix degrading enzymes, adhesion molecules, growth factor etc. This was in line with the reduction of the protein level of DNMT1 in FLS from RA patients which was also down-regulated in vitro by cytokines and growth factors stimulation [148,149]. This evidence concerns the gene DNMT1 and rheumatoid arthritis.