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Combinatory responses of proinflamamtory cytokines on nitric oxide-mediated function in mouse calvarial osteoblasts

Authors

  • Young-Guk Park,

    Corresponding author
    1. Department of Orthodondritics, Kyung-Hee University College of Dental Medicine, Dongdaemun-Gu, Seoul 130-701, Republic of Korea
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  • Kyung-Woon Kim,

    1. Department of Biological Sciences, SungKyunKwan University, 300 Chunchun-Dong, Suwon City, Kyunggi-Do 440-746, Republic of Korea
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  • Kwon-Ho Song,

    1. Department of Biological Sciences, SungKyunKwan University, 300 Chunchun-Dong, Suwon City, Kyunggi-Do 440-746, Republic of Korea
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  • Ji-Min Lee,

    1. Department of Biological Sciences, SungKyunKwan University, 300 Chunchun-Dong, Suwon City, Kyunggi-Do 440-746, Republic of Korea
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  • Jeong-Jin Hong,

    1. Department of Orthodondritics, Kyung-Hee University College of Dental Medicine, Dongdaemun-Gu, Seoul 130-701, Republic of Korea
    2. Department of Biological Sciences, SungKyunKwan University, 300 Chunchun-Dong, Suwon City, Kyunggi-Do 440-746, Republic of Korea
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  • Sungk-Kwon Moon,

    1. Department of Food and Biotechnology, Chungju National University, 123 Geomdan-ri Iryu-myeon, Chungju, Chungbuk 380-702, Republic of Korea
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  • Cheorl-Ho Kim

    Corresponding author
    1. Department of Biological Sciences, SungKyunKwan University, 300 Chunchun-Dong, Suwon City, Kyunggi-Do 440-746, Republic of Korea
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Fax: +82 2 960 7238. E-mail addresses: chkimbio@skku.edu, ygpark@khu.ac.kr

Tel.: +82 31 290 7002; fax: +82 31 290 7015.

Abstract

Combinatory responses of proinflamamtory cytokines have been examined on the nitric oxide-mediated function in cultured mouse calvarial osteoblasts. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) induced iNOS gene expression and NO production, although these actions were inhibited by L-NG-monomethylarginine (L-NMMA) and decreased alkaline phosphatase (ALPase) activity. Furthermore, NO donors, sodium nitroprusside (SNP) and NONOate dose-dependently elevated ALPase activity. In contrast, transforming-growth factor-β (TGF-β) decreased NO production stimulated by IL-1β, TNF-α and interferon-γ (IFN-γ). iNOS was expressed by mouse calvarial osteoblast cells after stimulation with IL-1β, TNF-α, and IFN-γ. Incubation of mouse calvarial osteoblast cells with the cytokines inhibited growth and ALPase activity. However, TGF-β-treatment abolished these effects of IL-1β, TNF-α and IFN-γ on growth inhibition and stimulation of ALPase in mouse calvarial osteoblast cells. In contrast, IL-1β, TNF-α, and IFN-γ exerted growth-inhibiting effects on mouse calvarial osteoblast cells which were partly NO-dependent. The results suggest that NO may act predominantly as a modulator of cytokine-induced effects on mouse calvarial osteoblast cells and TGF-β is a negative regulator of the NO production stimulated by IL-1β, TNF-α and IFN-γ.

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