Statins inhibit osteoblast migration by inhibiting Rac-Akt signaling
Statins inhibit osteoblast migration by inhibiting Rac-Akt signaling
复制标题
DOI：
10.1016/j.bbrc.2004.01.104
复制
发表时间：
2004-03-12
影响因子：
3.1
通讯作者：
Komori, T
中科院分区：
文献类型：
--
作者：
Fukuyama, R;Fujita, T;Komori, T
细胞迁移是骨组织修复和重塑的关键事件，但成骨细胞迁移的机制尚不清楚。他汀类药物是3-羟基-3-甲基戊二酰辅酶a还原酶的抑制剂，可以增加骨骼。然而，他汀类药物对成骨细胞迁移的影响尚不清楚。我们研究了氟伐他汀和美伐他汀对血小板衍生生长因子（PDGF）诱导的成骨细胞MC3T3-E1迁移的影响。PDGF促进成骨细胞迁移，而他汀类药物抑制PDGF诱导的迁移，甲羟戊酸和焦磷酸香叶基香叶基磷酸酯可消除他汀类药物的作用，而焦磷酸法尼基却不能。显性阴性Rac严重抑制pdgf诱导的成骨细胞迁移，降低Akt磷酸化。此外，氟伐他汀可降低Akt磷酸化水平，Akt抑制pdgf诱导的成骨细胞迁移。这些结果表明，他汀类药物抑制pdgf诱导的成骨细胞迁移，而Rac-Akt信号在成骨细胞迁移中起重要作用，并提示他汀类药物通过抑制Rac的香geranylgeranyation抑制Rac功能，从而导致Akt活化和成骨细胞迁移减少。(C) 2004爱思唯尔公司版权所有。
Cell migration is a key event in repair and remodeling of skeletal tissues, but the mechanism of osteoblast migration has not been resolved. Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, increase bone. However, the effect of statins on osteoblast migration remains to be clarified. We investigated the effect of fluvastatin and mevastatin on platelet-derived growth factor (PDGF)-induced migration of osteoblastic MC3T3-E1 cells. PDGF promoted osteoblast migration, while the statins inhibited PDGF-induced migration, and mevalonate and geranylgeranylpyrophosphate but not farnesylpyrophosphate abolished the effect of statins. Dominant-negative Rac severely inhibited PDGF-induced osteoblast migration and reduced Akt phosphorylation. Further, fluvastatin reduced Akt phosphorylation and dominant-negative Akt inhibited PDGF-induced osteoblast migration. These results demonstrate that statins inhibit PDGF-induced ostcoblast migration and Rac-Akt signaling plays an important role in the ostcoblast migration, and suggest that statins restrain Rac function by inhibiting geranylgeranylation of Rac, which leads to the reduction in Akt activation and osteoblast migration. (C) 2004 Elsevier Inc. All rights reserved.