Induction of osteoblast differentiation indices by statins in MC3T3‐E1 cells
- 3 May 2004
- journal article
- research article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 92 (3), 458-471
- https://doi.org/10.1002/jcb.20074
Abstract
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.Keywords
This publication has 35 references indexed in Scilit:
- Pitavastatin Enhanced BMP-2 and Osteocalcin Expression by Inhibition of Rho-Associated Kinase in Human OsteoblastsBiochemical and Biophysical Research Communications, 2001
- Simvastatin Promotes Osteoblast Differentiation and Mineralization in MC3T3-E1 CellsBiochemical and Biophysical Research Communications, 2001
- Compactin and Simvastatin, but Not Pravastatin, Induce Bone Morphogenetic Protein-2 in Human Osteosarcoma CellsBiochemical and Biophysical Research Communications, 2000
- Bone sialoprotein knockout mice have bone abnormalitiesBone, 1995
- Osteoblast and chondroblast differentiationBone, 1995
- Induction of vascular endothelial growth factor expression by prostaglandin E2 and E1 in osteoblasts.JCI Insight, 1994
- Expression of bone morphogenetic protein messenger RNA in prolonged cultures of fetal rat calvarial cellsJournal of Bone and Mineral Research, 1994
- Vasculotropin/Vascular Endothelial Growth Factor Induces Differentiation in Cultured OsteoblastsBiochemical and Biophysical Research Communications, 1994
- Relationship between collagen synthesis and expression of the osteoblast phenotype in MC3T3-E1 cellsJournal of Bone and Mineral Research, 1992
- Regulation of the mevalonate pathwayNature, 1990