Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells
Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells
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DOI：
10.1002/jcb.20074
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发表时间：
2004-06-01
影响因子：
4
通讯作者：
Horiuchi, N
中科院分区：
文献类型：
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作者：
Maeda, T;Matsunuma, A;Horiuchi, N
他汀类药物抑制3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶，该酶催化HMG-CoA转化为甲羟戊酸，这是胆固醇合成的限速步骤。本研究旨在了解他汀类药物诱导的成骨细胞分化事件。10（-7）M辛伐他汀显著增加非转化成骨细胞（MC 3 T3-E1）中骨形态发生蛋白-2（BMP-2）、血管内皮生长因子（VEGF）、碱性磷酸酶、I型胶原、骨唾液蛋白和骨钙素（OCN）的mRNA表达，同时抑制胶原酶-1和胶原酶-3的基因表达。在用10（-7）M辛伐他汀或10（-8）M西立伐他汀处理的细胞中，蛋白质如VEGF、OCN、胶原酶消化蛋白和非胶原蛋白的细胞外积累增加。在MC 3 T3-E1细胞的培养中，他汀类药物刺激矿化;用甲羟戊酸或香叶基香叶基焦磷酸（甲羟戊酸代谢产物）预处理MC 3 T3-E1细胞消除他汀类药物诱导的矿化。他汀类药物在体外刺激成骨细胞分化，可能成为未来治疗骨质疏松症的药物。(C)2004 Wiley-Liss，Inc.
Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes conversion of HMG-CoA to mevalonate, a rate-limiting step in cholesterol synthesis. The present study was undertaken to understand the events of osteoblast differentiation induced by statins. Simvastatin at 10(-7) M markedly increased mRNA expression for bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), alkaline phosphatase, type I collagen, bone sialoprotein, and osteocalcin (OCN) in nontransformed osteoblastic cells (MC3T3-E1), while suppressing gene expression for collagenase-1, and collagenase-3. Extracellular accumulation of proteins such as VEGF, OCN, collagenase-digestive proteins, and noncollagenous proteins was increased in the cells treated with 10(-7) M simvastatin, or 10(-8) M cerivastatin. In the culture of MC3T3-E1 cells, statins stimulated mineralization; pretreating MC3T3-E1 cells with mevalonate, or geranylgeranyl pyrophosphate (a mevalonate metabolite) abolished statin-induced mineralization. Statins stimulate osteoblast differentiation in vitro, and may hold promise drugs for the treatment of osteoporosis in the future. (C) 2004 Wiley-Liss, Inc.