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IL-18 Inhibits TNF-α-Induced Osteoclastogenesis Possibly via a T Cell-Independent Mechanism in Synergy with IL-12 In Vivo

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Abstract

It has recently been reported that tumor necrosis factor (TNF)-α has the ability to accelerate osteoclastogenesis. We previously reported that the proinflammatory cytokine interleukin (IL)-18 inhibits TNF-α-mediated osteoclastogenesis in mouse bone marrow cultures. In the present study, the effect of IL-18 on TNF-α-mediated osteoclastogenesis was investigated in vivo. We administered TNF-α with or without IL-18 into the supracalvaria of mice. The number of osteoclasts in the suture of the calvaria was increased in mice administered TNF-α. The number of osteoclasts in mice administered both TNF-α and IL-18 was lower than that in mice administered TNF-α alone. We previously showed that IL-12 and IL-18 synergistically inhibit TNF-α-mediated osteoclastogenesis in vitro. To assess the ability of these two cytokines to synergistically inhibit TNF-α-induced osteoclastogenesis in vivo, mice were administered the two cytokines at doses that did not inhibit osteoclast formation. The combination of IL-12 and IL-18 markedly inhibited TNF-α-induced osteoclastogenesis in vivo. To evaluate how IL-12 and IL-18 synergistically affect TNF-α-induced osteoclastogenesis, the IL-18 receptor (IL-18R) and IL-12R expression levels were analyzed by RT-PCR in bone marrow cells cultured with IL-12 or IL-18. IL-18R mRNA was increased in cells cultured with IL-12, while IL-12R mRNA was increased in cells cultured with IL-18. In addition, IL-18 inhibited TNF-α-induced osteoclastogenesis in mice with T-cell depletion caused by anti-CD4 and anti-CD8 antibodies. The present results suggest that IL-18 may inhibit TNF-α-mediated osteoclastogenesis in vivo via a T cell-independent mechanism.

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Acknowledgements

This work was supported by a Grant for Scientific Research from the Ministry of Education, Science, and Culture (Japan) and the President’s Discretionary Fund of Nagasaki University.

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Authors and Affiliations

  1. Department of Orthodontics and Dentofacial Orthopedics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Yukiko Morita, Masako Yoshimatsu, Yuji Fujimura, Haruka Kohara, Toshiko Eguchi & Noriaki Yoshida

  2. Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, 4-1 Seiryo, Aoba-ku, Sendai, 980-8575, Japan

    Hideki Kitaura

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  1. Yukiko Morita
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  2. Hideki Kitaura
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  3. Masako Yoshimatsu
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  4. Yuji Fujimura
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  5. Haruka Kohara
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  6. Toshiko Eguchi
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  7. Noriaki Yoshida
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Correspondence to Hideki Kitaura.

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The authors have stated that they have no conflict of interest.

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Morita, Y., Kitaura, H., Yoshimatsu, M. et al. IL-18 Inhibits TNF-α-Induced Osteoclastogenesis Possibly via a T Cell-Independent Mechanism in Synergy with IL-12 In Vivo. Calcif Tissue Int 86, 242–248 (2010). https://doi.org/10.1007/s00223-010-9335-6

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  • DOI: https://doi.org/10.1007/s00223-010-9335-6

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