IL-17A inhibits osteoclast differentiation of RANKL-stimulated RAW264.7 cells by suppressing JNK phosphorylation and c-Fos expression

Abstract

Periodontitis is a chronic inflammatory disease characterized by alveolar bone resorption. Inflammation-mediated bone loss is a major cause of various bone diseases, such as chronic periodontitis, and is due to an imbalance in bone remodeling that favors resorption. This imbalance is caused by increased inflammatory cytokines. Interleukin-17A (IL-17A) is a proinflammatory cytokine that is mainly secreted by activated T cells. IL-17A stimulates osteoclastic bone resorption via osteoblasts by inducing the expression of the receptor activator of NF-kB ligand (RANKL). However, little is known about the direct effects of IL-17A on the osteoclast precursors.
We confirmed that IL-17A suppresses the osteoclast differentiation of RAW264.7 cells in the presence of RANKL in a dose-dependent manner. We also found that treatment with SP 600125, a specific inhibitor of c-Jun N-terminal kinase (JNK), significantly inhibits the TRAP activity of RAW264.7 cells, which were stimulated by RANKL. In addition, we found that IL-17 A reduces the phosphorylation of JNK and expressions of c-Fos, which were increased by RANKL stimulation. These results suggest that IL-17A-induces inhibition of JNK phosphorylation and that expression of c-Fos may be one of the factors that suppresses the differentiation of osteoclast precursors into osteoclasts.