Effect of IL-12 on TNF-α -mediated osteoclast formation in bone marrow cells: Apoptosis mediated by Fas/Fas ligand interaction
Abstract
Recently, it has been found that differentiation into osteoclasts is induced by TNF-alpha. In this study, we investigated the effect of IL-12 on TNF-alpha-mediated osteoclastogenesis. When mouse bone marrow cells were cultured with TNF-alpha, osteoclast-like cells were formed. When they were cultured with both TNF-alpha and IL-12, the number of adherent cells in the bone marrow cells decreased in an IL-12 dose-dependent manner. A combination of IL-12 and TNF-alpha was necessary to induce death of the adherent cells in this culture system. Apoptotic alterations, which were indicated by morphological changes such as cellular atrophy, nuclear and cellular fragmentation, and biochemical changes such as DNA fragmentation, were observed in the adherent cells. Apoptosis of the adherent cells was markedly inhibited by anti-Fas ligand (FasL) Ab. RT-PCR and FACS analyses revealed that TNF-alpha up-regulated Fas transcription to lead to Fas expression on the surfaces of the adherent cells, whereas IL-12 could not induce Fas on the cells. In contrast, IL-12 induced FasL transcription to lead to FasL expression on the surfaces of nonadherent bone marrow cells, whereas TNF-alpha could not induce FasL on the cells. These results implied that apoptosis of the adherent cells in bone marrow cells might be caused by interaction between TNF-alpha-induced Fas on the adherent cells and IL-12-induced FasL on the nonadherent cells.
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IL-12 added to TNF-α-stimulated cultures induces osteoclast apoptosis by upregulating expression of Fas/Fas ligands.
“Using mouse bone marrow cultures, Kitaura and associates found that IL-12 when added to TNF-α-stimulated cultures induced osteoclast apoptosis by upregulating their expression of Fas/Fas ligands [45].”
From Osteoclasts and Microgravity (2020) · cites this paper as [45]
Cites
Lam, J., Takeshita, S., Barker, J. E., Kanagawa, O., Ross, F. P., & Teitelbaum, S. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci11176 · Cited by 1,440 · cited 1× · see citing works
“In contrast, another group indicated that TNF- alone, at any concentration, fails to induce the differentiation of murine osteoclast precursors and that, rather, TNF- dramatically enhances in vitro osteoclastogenesis primed by a low dose of RANKL that is insufficient to induce osteoclast formation (32).”
BackgroundThe Functional Block of TNF but Not of IL-6 Prevents Bone Loss in Ovariectomized Mice
Kimble, R. B., Bain, S., & Pacifici, R. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.6.935 · Cited by 241 · see citing works
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Smith, J. K. (2020) · Life · doi:10.3390/life10090207 · Cited by 52 · see citing works
“Using mouse bone marrow cultures, Kitaura and associates found that IL-12 when added to TNF-α-stimulated cultures induced osteoclast apoptosis by upregulating their expression of Fas/Fas ligands [45].”
BackgroundMorita, Y., Kitaura, H., Yoshimatsu, M., Fujimura, Y., Kohara, H., Eguchi, T., & Yoshida, N. (2010) · Calcified Tissue International · doi:10.1007/s00223-010-9335-6 · Cited by 39 · see citing works
Self-citation
- Authors
- Kitaura, H., Nagata, N., Fujimura, Y., Hotokezaka, H., Yoshida, N., & Nakayama, K.
- Affiliations
- Nagasaki University (JP)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-11-01
- Volume
- 169
- Issue
- 9
- Pages
- 4732-4738
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2140434807
- Cited by
- 72
- References
- 2
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2022: 1 · 2021: 2 · 2020: 7 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 3 · 2012: 4
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-12, TNF-α, osteoclastogenesis, apoptosis, Fas/Fas ligand interaction, bone marrow cells, Fas expression, Fas ligand expression, DNA fragmentation, adherent cells
- MeSH terms
- Animals, Benzimidazoles, Bone Marrow Cells, Cell Differentiation, Cell Nucleus, Cells, Cultured, Fluorescent Dyes, Ligands, Macrophages, Male, Membrane Glycoproteins, Osteoclasts, Tumor Necrosis Factor-alpha, Macrophage Colony-Stimulating Factor, Apoptosis, Interleukin-12, fas Receptor, Mice, Fas Ligand Protein, DNA Fragmentation
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