RRC ID 1380
著者 Fukuyama R, Fujita T, Azuma Y, Hirano A, Nakamuta H, Koida M, Komori T.
タイトル Statins inhibit osteoblast migration by inhibiting Rac-Akt signaling.
ジャーナル Biochem Biophys Res Commun
Abstract 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 osteoblast migration and Rac-Akt signaling plays an important role in the osteoblast migration, and suggest that statins restrain Rac function by inhibiting geranylgeranylation of Rac, which leads to the reduction in Akt activation and osteoblast migration.
巻・号 315(3)
ページ 636-42
公開日 2004-3-12
DOI 10.1016/j.bbrc.2004.01.104
PII S0006291X04001536
PMID 14975748
MeSH Animals Cell Line Chemotaxis / drug effects* Chemotaxis / physiology Chromones / pharmacology Enzyme Inhibitors / pharmacology Fatty Acids, Monounsaturated / pharmacology* Fluvastatin Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology* Indoles / pharmacology* Insulin-Like Growth Factor I / pharmacology Lovastatin / analogs & derivatives* Lovastatin / pharmacology* Mice Morpholines / pharmacology Osteoblasts / cytology Osteoblasts / drug effects* Osteoblasts / enzymology Phosphorylation Platelet-Derived Growth Factor / antagonists & inhibitors Platelet-Derived Growth Factor / pharmacology Polyisoprenyl Phosphates / pharmacology Protein Serine-Threonine Kinases* Proto-Oncogene Proteins / antagonists & inhibitors* Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-akt Recombinant Proteins / antagonists & inhibitors Recombinant Proteins / pharmacology Sesquiterpenes Signal Transduction / drug effects Signal Transduction / physiology Toxins, Biological / pharmacology Vascular Endothelial Growth Factor A / pharmacology rac GTP-Binding Proteins / antagonists & inhibitors* rac GTP-Binding Proteins / metabolism rho GTP-Binding Proteins / antagonists & inhibitors rho GTP-Binding Proteins / metabolism
IF 2.985
引用数 40
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)