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IL-33 Inhibits TNF-α-Induced Osteoclastogenesis and Bone Resorption

Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 1130;
Received: 25 December 2019 / Revised: 3 February 2020 / Accepted: 5 February 2020 / Published: 8 February 2020
(This article belongs to the Special Issue Molecular Mechanisms Regulating Osteoclastogenesis)
Interleukin (IL)-33 is a member of the IL-1 family, which acts as an alarmin. Several studies suggested that IL-33 inhibited osteoclastogenesis and bone resorption. Tumor necrosis factor-α (TNF-α) is considered a direct inducer of osteoclastogenesis. However, there has been no report regarding the effect of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. The objective of this study is to investigate the role of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. In an in vitro analysis of osteoclastogenesis, osteoclast precursors, which were derived from bone marrow cells, were treated with or without IL-33 in the presence of TNF-α. Tartrate-resistant acid phosphatase (TRAP) staining solution was used to assess osteoclast formation. In an in vivo analysis of mouse calvariae, TNF-α with or without IL-33 was subcutaneously administrated into the supracalvarial region of mice daily for 5 days. Histological sections were stained for TRAP, and osteoclast numbers were determined. Using micro-CT reconstruction images, the ratio of bone destruction area on the calvariae was evaluated. The number of TRAP-positive cells induced by TNF-α was significantly decreased with IL-33 in vitro and in vivo. Bone resorption was also reduced. IL-33 inhibited IκB phosphorylation and NF-κB nuclear translocation. These results suggest that IL-33 inhibited TNF-α-induced osteoclastogenesis and bone resorption. View Full-Text
Keywords: osteoclastogenesis; osteoclast; IL-33; TNF-α osteoclastogenesis; osteoclast; IL-33; TNF-α
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Ohori, F.; Kitaura, H.; Ogawa, S.; Shen, W.-R.; Qi, J.; Noguchi, T.; Marahleh, A.; Nara, Y.; Pramusita, A.; Mizoguchi, I. IL-33 Inhibits TNF-α-Induced Osteoclastogenesis and Bone Resorption. Int. J. Mol. Sci. 2020, 21, 1130.

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