TY - JOUR JO - Central European Journal of Immunology SN - 1426-3912 VL - 43 IS - 2 PY - 2018 ID - Yago2018 TI - IL-35 inhibits human osteoclastogenesis from monocytes induced by receptor-activator of NF-κB ligand AB - IL-35 is known as a regulatory cytokine produced by regulatory T cells. It has also been reported that IL-35 suppresses the proliferation of Th17 cells, which is involved in the pathogenesis of many autoimmune diseases. However, in rheumatoid arthritis patients, the role of IL-35 is controversial, and the role of IL-35 in bone metabolism has not been clarified. We investigated the effect of IL-35 on human osteoclast differentiation and activation. We first evaluated the effect of rhIL-35 on human osteoclastogenesis from monocytes cultured alone, induced by soluble-RANKL. We also examined the role of IL-35 on the bone-resorption function of mature osteoclasts. Furthermore, we analysed the molecular mechanism of IL-35 function in monocytes or pre-osteoclasts using RT-PCR. rhIL-35 significantly inhibited human osteoclastogenesis in a dose-dependent manner. In addition, rhIL-35 also significantly decreased the area of pit formation by mature osteoclasts. rhIL-35 significantly decreased mRNA expression of RANK in monocytes and RANK and FOS in pre-osteoclasts. Our current findings suggest that IL-35 inhibits osteoclastogenesis and osteoclast activation by inhibiting both RANK and FOS. IL-35 also has an inhibitory effect on osteoclastic-bone resorption, suggesting that IL-35 may have a therapeutic potential for RA. AU - Yago, Toru AU - Nanke, Yuki AU - Kawamoto, Manabu AU - Kobashigawa, Tsuyoshi AU - Yamanaka, Hisashi AU - Kotake, Shigeru SP - 148 EP - 154 DA - 2018 DO - 10.5114/ceji.2018.77384 UR - http://dx.doi.org/10.5114/ceji.2018.77384 ER -