title: Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells.
abstract: The cholesterol-lowering drug, simvastatin, is a pro-drug of a potent 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor and inhibits cholesterol synthesis in humans and animals. In addition, the bone effects of statins including simvastatin are being studied. We assessed the effects of simvastatin on osteoblastic differentiation in nontransformed osteoblastic cells (MC3T3-E1) and rat bone marrow cells. Simvastatin enhanced alkaline phosphatase (ALP) activity and mineralization in a dose- and time-dependent fashion. This stimulatory effect of the statin was observed at relatively low doses (significant at 10(-8) M and maximal at 10(-7) M). Northern blot analysis showed that the statin (10(-7) M) increased in bone morphogenetic protein-2 as well as ALP mRNA concentrations in MC3T3-E1 cells. Simvastatin (10(-7) M) slightly increased in type I collagen mRNA abundance throughout the culture period, whereas it markedly inhibited the gene expression of collagenase-1 between days 14 and 22 of culture. These results indicate that simvastatin has anabolic effects on bone through the promotion of osteoblastic differentiation, suggesting that it could be used for the treatment of common metabolic bone diseases such as osteoporosis.
authors.affiliation: Department of Biochemistry, Ohu University School of Dentistry, Koriyama 963-8611, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.forename: A
authors.initials: A
authors.lastname: Matsunuma
authors.forename: T
authors.initials: T
authors.lastname: Kawane
authors.forename: N
authors.initials: N
authors.lastname: Horiuchi
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D051379:Mice; D008903:Minerals / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D019821:Simvastatin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta
chemical_list: D000924:Anticholesteremic Agents; C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008903:Minerals; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019821:Simvastatin; D000469:Alkaline Phosphatase