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Cited by 39Bone Metabolism and DiseasesRheumatoid Arthritis Research and TherapiesOsteomyelitis and Bone Disorders Research

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

Morita, Yukiko, Kitaura, Hideki, Yoshimatsu, Masako, Fujimura, Yuji, Kohara, Haruka, Eguchi, Toshiko, Yoshida, Noriaki·2010·Calcified Tissue International
DOI 10.1007/s00223-010-9335-6
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Abstract

It has recently been reported that tumor necrosis factor (TNF)-alpha has the ability to accelerate osteoclastogenesis. We previously reported that the proinflammatory cytokine interleukin (IL)-18 inhibits TNF-alpha-mediated osteoclastogenesis in mouse bone marrow cultures. In the present study, the effect of IL-18 on TNF-alpha-mediated osteoclastogenesis was investigated in vivo. We administered TNF-alpha 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-alpha. The number of osteoclasts in mice administered both TNF-alpha and IL-18 was lower than that in mice administered TNF-alpha alone. We previously showed that IL-12 and IL-18 synergistically inhibit TNF-alpha-mediated osteoclastogenesis in vitro. To assess the ability of these two cytokines to synergistically inhibit TNF-alpha-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-alpha-induced osteoclastogenesis in vivo. To evaluate how IL-12 and IL-18 synergistically affect TNF-alpha-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-alph…

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  • IL-12 enhances the ability of IL-18 to inhibit TNF-α-mediated osteoclastogenesis, and the inhibition is T-cell independent.

    “Using injections of TNF-α alone and with IL-18 or IL-18 + IL-12 into live murine supracalvaria, Morita and associates found that IL-12 enhanced IL-18s ability to inhibit TNF-α-mediated osteoclastogenesis and that the inhibition was T-cell independent [46].”

    From Osteoclasts and Microgravity (2020) · cites this paper as [46]

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Authors
Morita, Y., Kitaura, H., Yoshimatsu, M., Fujimura, Y., Kohara, H., Eguchi, T., & Yoshida, N.
Affiliations
  • Nagasaki University (JP)
  • Tohoku University (JP)
Corresponding author
Kitaura, Hideki
ORCID
Venue
Calcified Tissue International
Publisher
Springer Science and Business Media LLC
Published
2010-01-29
Volume
86
Issue
3
Pages
242-248
ISSN
  • 0171-967X (ISSN-L)
  • 1432-0827
DOI
10.1007/s00223-010-9335-6
OpenAlex
W1990654188
Cited by
39
References
26
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 5 · 2018: 3 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 4
FWCI
1.43
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Calcified Tissue International (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
Keywords
IL-18, IL-12, TNF-α, osteoclastogenesis, cytokine synergy, IL-18 receptor, IL-12 receptor, T cell depletion, calvaria, bone resorption
MeSH terms
Animals, Bone Resorption, Cell Count, Cell Differentiation, Cells, Cultured, Dose-Response Relationship, Drug, Drug Synergism, Male, Mice, Inbred C57BL, Osteoclasts, RNA, Messenger, Stem Cells, T-Lymphocytes, Tumor Necrosis Factor-alpha, Up-Regulation, Bone Remodeling, Interleukin-12, Interleukin-18, Cell Proliferation, Mice, Receptors, Interleukin-12, Receptors, Interleukin-18

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