Background Overexpression of the components of the Janus kinase/signal transducer and activator of transcription (JAK/ STAT) signalling pathway is the key factor of the pathogenic mechanisms underlying systemic juvenile idiopathic arthritis (sJIA).The study aims to investigate the association between miR-21 and the JAK/STAT signal pathway in JIA.Methods Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) in active JIA patients.The relative expressions of miR-21,STAT3 and suppressor of cytokine signalling 3 in PBMCs were measured by real-time polymerase chain reaction and their expressions were measured by western blotting and dual-luciferase reported assay.Rheumatoid arthritis fibroblast-like synovial cell (RASF) was stimulated to become to osteoclasts using macrophage colony-stimulating factor (M-CSF) and factors that can impact on their differentiation ability were identified through the transfection of LV3-miR-21.The expression of STAT3/p-STAT3 was measured by western blot,and the levels of interleukin (IL)-17A,p65,matrix metalloproteinases (MMP)-3,MMP-4 and receptor activator of nuclear factor-κd3 after the LV3-miR-21 transfection were tested by enzyme-linked immunosorbent assay.Finally,the miR-21 targeted STAT3 gene was detected by the dualluciferase reported assay.Results The expression of miR-21 was significantly lower in JIA patients than in healthy control (P ＜ 0.05).The level of STAT3 was increased in PBMCs of JIA group compared with control group (P ＜ 0.05).Furthermore,the expression levels of miR-21 in sJIA and polyarticular JIA groups were negatively correlated with STAT3 (r=-0.5854/r=-0.6134,P ＜ 0.05).The expression of STAT3 changed little in PBMCS after the stimulation of IL-6 and not in RASFs with transfection of LV3-miR-21.The expression of p-STAT3 decreased after the stimulation of IL-6 in RASFs transfected by LV3-miR-21 (P ＜ 0.05).RASFs were induced into osteoclasts using M-CSF.The number of osteoclasts as determined by tartrate-resistant acid phosphatase staining was significantly lower in group miR-21 mimics as compared with the negative control group (P ＜ 0.05).Conclusions We showed that expression of miR-21 was significantly lower in JIA patients compared with healthy control.MiR-21 might affect the JAK/STAT signal pathway by suppressing the expression of STAT3 and phosphorylation of STAT3.MiR-21 could inhibit the production of osteoclasts induced from RASFs by M-CSF.