Inhibitory Effect of Vitamin K2 on Interleukin-1β-Stimulated Proliferation of Human Osteoblasts
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概要
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The effect of the proinflammatory cytokine interleukin (IL)-1β on the cellular proliferation of human osteoblastic cells (SaM-1) and osteosarcoma-derived cells (SaOS-2, HOS, and MG-63) was examined. IL-1β stimulated the proliferation of SaM-1 and MG-63 cells, but had no effect on that of SaOS-2 or HOS cells. Using reverse transcription-polymerase chain reaction (RT-PCR) analysis, the mRNA expression of IL-1 receptor type I (IL-1R1) was detected in SaM-1 and MG-63 cells consistently, but not in SaOS-2 or HOS cells in the proliferative stage. Neither the decoy inhibitory IL-1 receptor type II (IL-1R2) nor IL-1R antagonist mRNA was detected in any of the cell lines, suggesting that IL-1β stimulated proliferation via IL-1R1. The IL-1β -stimulated proliferation was inhibited by the MAPK kinase (MEK) inhibitor PD98059 but not by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 or the cyclooxygenase-2 specific inhibitor NS-398, suggesting that IL-1β stimulated proliferation via MEK, without affecting prostaglandin E2 synthesis. IL-1β stimulated cellular proliferation but inhibited the synthesis of osteocalcin containing γ-carboxylated glutamic acid (Gla-OSCAL). Both the increased proliferation and decreased Gla-OSCAL synthesis were suppressed by vitamin K2 (VK2), which is a cofactor for γ-carboxylase. Furthermore, the inhibitory effect of VK2 on IL-1β -stimulated proliferation was suppressed by warfarin. However, rifampicin the nuclear receptor steroid and xenobiotic receptor (SXR) ligand had no effect of IL-b , suggesting that IL-1β is involved in VK2 dependent γ-calboxylation but not SXR-activation. These results suggest that IL-1β stimulated cellular proliferation via MEK and inhibited Gla-OSCAL synthesis, which were both inhibited by VK2 via γ-carboxylation.
著者
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戸苅 彰史
愛知学院大学歯学部薬理学講座
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Matsuda Tomohiro
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University
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Kondo Ayami
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University
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Tsunashima Yoshihiko
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University
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Togari Akifumi
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University
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Togari Akifumi
Department Of Pharmacology School Of Dentistry Aichi-gakuin University
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Togari Akifumi
Departments Of Pharmacology School Of Dentistry Aichi-gakuin University
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Togari Akifumi
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Nagoya City University
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Togari Akifumi
Departments Of Anatomy Pharmacology School Of Dentistry Aichi-gakuin University
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戸苅 彰史
名古屋市立大学薬学部薬品作用学教室
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Matsuda Tomohiro
Department Of Epidemiology National Institute Of Public Health
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