RRC ID 18924
著者 Matsuda T, Kondo A, Tsunashima Y, Togari A.
タイトル Inhibitory effect of vitamin K(2) on interleukin-1beta-stimulated proliferation of human osteoblasts.
ジャーナル Biol Pharm Bull
Abstract The effect of the proinflammatory cytokine interleukin (IL)-1beta on the cellular proliferation of human osteoblastic cells (SaM-1) and osteosarcoma-derived cells (SaOS-2, HOS, and MG-63) was examined. IL-1beta 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-1beta stimulated proliferation via IL-1R1. The IL-1beta -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-1beta stimulated proliferation via MEK, without affecting prostaglandin E(2) synthesis. IL-1beta stimulated cellular proliferation but inhibited the synthesis of osteocalcin containing gamma-carboxylated glutamic acid (Gla-OSCAL). Both the increased proliferation and decreased Gla-OSCAL synthesis were suppressed by vitamin K(2) (VK(2)), which is a cofactor for gamma-carboxylase. Furthermore, the inhibitory effect of VK(2) on IL-1beta -stimulated proliferation was suppressed by warfarin. However, rifampicin the nuclear receptor steroid and xenobiotic receptor (SXR) ligand had no effect of IL-beta, suggesting that IL-1beta is involved in VK(2) dependent gamma-calboxylation but not SXR-activation. These results suggest that IL-1beta stimulated cellular proliferation via MEK and inhibited Gla-OSCAL synthesis, which were both inhibited by VK(2) via gamma-carboxylation.
巻・号 33(5)
ページ 804-8
公開日 2010-1-1
DOI 10.1248/bpb.33.804
PII JST.JSTAGE/bpb/33.804
PMID 20460758
MeSH Adult Anticoagulants Bone Neoplasms / drug therapy Bone Neoplasms / metabolism Cell Line Cell Proliferation* / drug effects Cyclooxygenase 2 / metabolism Cyclooxygenase Inhibitors Dinoprostone / biosynthesis Enzyme Inhibitors Flavonoids / pharmacology Glutamic Acid / biosynthesis Humans Imidazoles / pharmacology Interleukin-1 / metabolism Interleukin-1beta / genetics Interleukin-1beta / metabolism* Male Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinase Kinases / metabolism* Nitrobenzenes / pharmacology Osteoblasts / cytology Osteoblasts / drug effects Osteoblasts / metabolism* Osteocalcin / metabolism* Osteosarcoma / drug therapy Osteosarcoma / metabolism Pregnane X Receptor Protein Kinase Inhibitors / metabolism Pyridines / pharmacology RNA, Messenger / metabolism Receptors, Steroid / metabolism Reverse Transcriptase Polymerase Chain Reaction Rifampin / pharmacology Sulfonamides / pharmacology Vitamin K / pharmacology* Vitamins / pharmacology* Warfarin / pharmacology Young Adult p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
IF 1.863
引用数 5
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 HOS(RCB0992) Saos-2(RCB0428)