Interleukin 26 suppresses receptor activator of nuclear factor κB ligand induced osteoclastogenesis via down-regulation of nuclear factor of activated T-cells, cytoplasmic 1 and nuclear factor κB activity.

Abstract

IL-26 has been shown to have high expression in RA. However, the effects of IL-26 on bone destruction in RA have not been evaluated. The aim of this study was to investigate the effects and mechanisms of IL-26 on RANK ligand (RANKL)-induced osteoclastogenesis. We treated cells with IL-26 in RANKL-induced oseteoclastogenesis to monitor osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. Osteoclast activity was assessed by pit formation assay and F-actin ring formation. The mechanism of the inhibition was studied by biochemical analyses such as RT-PCR, immunofluorescence staining and immunoblotting. In addition, cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. IL-26 inhibited RANKL-induced TRAP-positive multinucleated cells and inhibited RANKL-induced nuclear factor κB (NF-κB) activation and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) nuclear translocation in RAW264.7 cells. Also, IL-26 significantly inhibited the bone-resorbing activity and F-actin ring formation ability of mature osteoclasts. Moreover, IL-26 suppressed RANKL-induced mitogen-activated protein kinase activation and NFATc1 downstream gene expression. We suggest that the inhibitory activity of IL-26 on osteoclastogenesis is via down-regulation of RANKL-induced NF-κB and NFATc1 expression. Our results suggest IL-26 as a possible new remedy against osteolytic bone destruction.