Interleukin-17 inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing nuclear factor-κB p65 phosphorylation and nuclear factor of activated T cells c1 expression

Background Bone is constantly being regenerated while maintaining dynamic homeostasis through a delicate balance between bone destruction by osteoclasts and bone formation by osteoblasts, a process known as bone remodeling. Bone resorption on the compression side is closely related to the differentiation and activation of osteoclasts. Interleukin-17 (IL-17) is a pro-inflammatory cytokine secreted by Th17 cells and other cells. IL-17 has been shown to indirectly induce osteoclast differentiation by increasing the expression of receptor activator of NFκB ligand (RANKL) in osteoblasts. However, little has been reported about the effect of IL-17 directly acting on osteoclast precursor cells during osteoclast differentiation. This study aimed to investigate the effect of IL-17 on RANKL-induced osteoclast differentiation in RAW264.7 cells. Results Osteoclast differentiation and formation were assessed by measuring tartrate-resistant acid-phosphatase (TRAP) activity. RANKL stimulation enhanced TRAP activity in RAW264.7 cells, but co-stimulation with IL-17 attenuated it. RANKL stimulation activated the canonical NF-κB pathway, leading to increased phosphorylation of NF-κB p65 and its subsequent nuclear translocation, but IL-17 suppressed this increased phosphorylation and nuclear translocation of NF-κB p65. c-Fos and nuclear factor of activated T cells (NFATc1), nuclear transcription factors that play important roles in regulating the expression of many osteoclast-specific genes involved in osteoclast differentiation, were induced by RANKL stimulation. IL-17 reduced RANKL-stimulated c-Fos and NFATc1 expression. Conclusions IL-17 acts directly on RAW264.7 cells, inhibiting the RANKL/RANK signal-induced phosphorylation of NF-κB p65 and its subsequent nuclear translocation. This study provides evidence suggesting that the mechanism by which IL-17 suppresses RANKL-induced osteoclast differentiation may involve the suppression of c-Fos and NFATc1 expression, key transcription factors that control osteoclast formation, by inhibiting the activation of NF-κB p65.