IL-17 Down-regulates RANKL-induced Osteoclast Differentiation from RAW264.7 Cells

Abstract

In orthodontic treatment, tooth movement occurs based on bone remodeling in response to orthodontic forces. Interleukin-17A (IL-17) is a proinflammatory cytokine that is primarily secreted by Th 17 cells. In the present study, we investigated the mechanisms by which transforming growth factor β-activated kinase 1 (TAK1) inhibits osteoclast differentiation and the role of IL-17 in the intracellular signaling pathways IκB kinase α (IKKα) and nuclear factor-κB (NF-κB) p65, which are downstream of mitogen-activated protein kinases (MAPKs) (p38 and c-Jun N-terminal kinases (JNK)). We confirmed that IL-17 dose-dependently suppressed tartrate-resistant acid phosphatase (TRAP) activity in RAW264.7 cells in the presence of receptor for activation of NF-κB ligand (RANKL). We also found that a treatment with takinib, a potent and selective TAK1 inhibitor, significantly inhibited RANKL-stimulated TRAP activity in RAW264.7 cells. Furthermore, we demonstrated that IL-17 reduced the phosphorylation of TAK1, IKKα, and NF-κB p65. Collectively, these results suggest that IL-17 suppressed RANKL-induced osteoclast differentiation by inhibiting the canonical NF-κB pathway via TAK1. Therefore, IL-17 may be one of the factors suppressing RANKL-induced osteoclast differentiation. In the future, we would like to contribute to the development of reagents that locally control osteoclast differentiation by combining with nanocapsules that selectively deliver IL-17 to osteoclast progenitor cells.