Costimulation of Murine Osteoblasts with Interferon-γ and Tumor Necrosis Factor-α Induces Apoptosis through Downregulation of Bcl-2 and Release of Cytochrome c from Mitochondria
During chronic inflammation from diseases, such as periodontal disease, the proinflammatory cytokines interferon-gamma (IFNγ) and tumor necrosis factor-α (TNFα) alter bone remodeling. To elucidate the underlying molecular mechanisms, we investigated the effect of IFNγ and TNFα on the proliferation a...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2018/3979606 |
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| _version_ | 1832554537970302976 |
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| author | Mayumi Iguchi Miki Hiroi Haruhide Kanegae Yoshihiro Ohmori |
| author_facet | Mayumi Iguchi Miki Hiroi Haruhide Kanegae Yoshihiro Ohmori |
| author_sort | Mayumi Iguchi |
| collection | DOAJ |
| description | During chronic inflammation from diseases, such as periodontal disease, the proinflammatory cytokines interferon-gamma (IFNγ) and tumor necrosis factor-α (TNFα) alter bone remodeling. To elucidate the underlying molecular mechanisms, we investigated the effect of IFNγ and TNFα on the proliferation and survival of clonal MC3T3-E1 mouse osteoblasts. We found that although IFNγ or TNFα alone affected cell growth and survival only marginally, costimulation with both synergistically inhibited cell growth and reduced cell viability. The diminished cell viability was due to apoptosis, as indicated by increased TUNEL staining and elevated caspase 3, 8, and 9 activities. Western blot also showed that costimulation with IFNγ and TNFα elicited cytochrome c release and downregulated B cell lymphoma 2 (Bcl-2) expression without affecting Bcl-2-associated X (Bax) protein expression. Furthermore, stable Bcl-2 overexpression significantly alleviated cell death following costimulation. Collectively, these results suggested that IFNγ and TNFα elicited osteoblast apoptosis via cytochrome c release from damaged mitochondria, caspase activation, and Bcl-2 downregulation. |
| format | Article |
| id | doaj-art-f85aa99e4493496e87c9d35c0797f681 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-f85aa99e4493496e87c9d35c0797f6812025-02-03T05:51:18ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/39796063979606Costimulation of Murine Osteoblasts with Interferon-γ and Tumor Necrosis Factor-α Induces Apoptosis through Downregulation of Bcl-2 and Release of Cytochrome c from MitochondriaMayumi Iguchi0Miki Hiroi1Haruhide Kanegae2Yoshihiro Ohmori3Division of Orthodontics, Department of Human Development and Fostering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, JapanDivision of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, JapanDivision of Orthodontics, Department of Human Development and Fostering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, JapanDivision of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, JapanDuring chronic inflammation from diseases, such as periodontal disease, the proinflammatory cytokines interferon-gamma (IFNγ) and tumor necrosis factor-α (TNFα) alter bone remodeling. To elucidate the underlying molecular mechanisms, we investigated the effect of IFNγ and TNFα on the proliferation and survival of clonal MC3T3-E1 mouse osteoblasts. We found that although IFNγ or TNFα alone affected cell growth and survival only marginally, costimulation with both synergistically inhibited cell growth and reduced cell viability. The diminished cell viability was due to apoptosis, as indicated by increased TUNEL staining and elevated caspase 3, 8, and 9 activities. Western blot also showed that costimulation with IFNγ and TNFα elicited cytochrome c release and downregulated B cell lymphoma 2 (Bcl-2) expression without affecting Bcl-2-associated X (Bax) protein expression. Furthermore, stable Bcl-2 overexpression significantly alleviated cell death following costimulation. Collectively, these results suggested that IFNγ and TNFα elicited osteoblast apoptosis via cytochrome c release from damaged mitochondria, caspase activation, and Bcl-2 downregulation.http://dx.doi.org/10.1155/2018/3979606 |
| spellingShingle | Mayumi Iguchi Miki Hiroi Haruhide Kanegae Yoshihiro Ohmori Costimulation of Murine Osteoblasts with Interferon-γ and Tumor Necrosis Factor-α Induces Apoptosis through Downregulation of Bcl-2 and Release of Cytochrome c from Mitochondria Mediators of Inflammation |
| title | Costimulation of Murine Osteoblasts with Interferon-γ and Tumor Necrosis Factor-α Induces Apoptosis through Downregulation of Bcl-2 and Release of Cytochrome c from Mitochondria |
| title_full | Costimulation of Murine Osteoblasts with Interferon-γ and Tumor Necrosis Factor-α Induces Apoptosis through Downregulation of Bcl-2 and Release of Cytochrome c from Mitochondria |
| title_fullStr | Costimulation of Murine Osteoblasts with Interferon-γ and Tumor Necrosis Factor-α Induces Apoptosis through Downregulation of Bcl-2 and Release of Cytochrome c from Mitochondria |
| title_full_unstemmed | Costimulation of Murine Osteoblasts with Interferon-γ and Tumor Necrosis Factor-α Induces Apoptosis through Downregulation of Bcl-2 and Release of Cytochrome c from Mitochondria |
| title_short | Costimulation of Murine Osteoblasts with Interferon-γ and Tumor Necrosis Factor-α Induces Apoptosis through Downregulation of Bcl-2 and Release of Cytochrome c from Mitochondria |
| title_sort | costimulation of murine osteoblasts with interferon γ and tumor necrosis factor α induces apoptosis through downregulation of bcl 2 and release of cytochrome c from mitochondria |
| url | http://dx.doi.org/10.1155/2018/3979606 |
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