Nano Biomedicine
ORIGINAL ARTICLE

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

 Akito FUKAWA1, Hiroshi INOUE2, Aki NISHIURA3,
Seiji GODA2, and Naoyuki MATSUMOTO3

 1Graduate School of Dentistry, Department of Orthodontics,
2Department of Physiology, 3Department of Orthodontics, Osaka Dental University, Osaka, Japan
Nano Biomed 2023; 15(2):66-74 (Dec 30, Nano Biomedicine)
Synopsis
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-κpathway 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.

Key words: IL-17, RANKL, osteoclast differentiation


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DOI : "https://doi.org/10.11344/nano.15.66"

J-stage : Fukawa A, Inoue H, Nishimura A, Goda S, Matsumoto N. IL-17 down-regulates RANKL-induced osteoclast differentiation from RAW264.7 cells. Nano Biomed 2023; 15: 66-74.