The effect of the IL-6/sIL-6R complex on RANKL, JAK2, STAT3 in fibroblast-like synoviocytes (FLS). (A) Stimulation of FLS with IL-6 and sIL-6R at several different concentrations (0, 30, 50, 100 ng of both) for 30 minutes induced RANKL protein expression in a dose-dependent manner. In contrast, expression of OPG protein was gradually inhibited under the same conditions. (B) Treatment with IL-6/sIL-6R (100 ng of both) for 30 minutes in control synoviocytes increased the expression of SOCS3, p-JAK2, p-STAT3, and RANKL proteins. In SOCS3-siRNA transfected FLS, expression of p-JAK2, p-STAT3, and RANKL under IL-6/sIL-6R stimulation (100 ng/ml each) for 30 minutes was significantly increased compared to control synoviocytes. Data are determined in three independent experiments. IL-6, interleukin-6; JAK2, Janus activated kinase; OPG, osteoprotegerin; RANKL, receptor activator of NF-κB ligand; sIL-6R, soluble interleukin-6 receptor; SOCS3, suppressor of cytokine signaling 3; STAT3, signal transducer and activator of transcription-3.