Nonetheless, the potential pathogenetic role of hyper-methylation has been recently demonstrated, as hyper-methylation of MEG3 (Maternally Expressed 3) gene, with consequent hyperexpression of nucleotide oligomerization domain (NOD)-like receptors 5 (NLRC5), that plays a role in immunoinflammatory and autoimmune responses, has been observed both in Complete Freund’s Adjuvant (CFA)-induced synovial tissues in rodent RA and fibroblast-like synoviocytes and the effects were counteracted by DAC in vitro [45]. Here, MEG3 is linked to rheumatoid arthritis.