## Abstract The orphan nuclear receptor Nurr1 is primarily expressed in the central nervous system. It has been shown that Nurr1 is necessary for terminal differentiation of dopaminergic (DA) neurons in ventral midbrain. The receptor, however, is also expressed in other organs including bone, even
Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells
✍ Scribed by Toyonobu Maeda; Ayako Matsunuma; Izuru Kurahashi; Toru Yanagawa; Hiroshi Yoshida; Noboru Horiuchi
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 261 KB
- Volume
- 92
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
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. © 2004 Wiley‐Liss, Inc.
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