文章基本信息

标题：Inhibitory Effect of Vitamin K2 on Interleukin-1β-Stimulated Proliferation of Human Osteoblasts
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作者：Tomohiro Matsuda ; Ayami Kondo ; Yoshihiko Tsunashima 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2010
卷号：33
期号：5
页码：804-808
DOI：10.1248/bpb.33.804
出版社：The Pharmaceutical Society of Japan
摘要：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.
关键词：interleukin-1β;proliferation;osteoblast;osteocalcin;γ-carboxylation;vitamin K2