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Induction of osteoblast differentiation indices by statins in MC3T3‐E1 cells
Author(s) -
Maeda Toyonobu,
Matsunuma Ayako,
Kurahashi Izuru,
Yanagawa Toru,
Yoshida Hiroshi,
Horiuchi Noboru
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20074
Subject(s) - geranylgeranyl pyrophosphate , osteocalcin , osteoblast , bone sialoprotein , cerivastatin , simvastatin , chemistry , collagenase , statin , bone morphogenetic protein 2 , alkaline phosphatase , hmg coa reductase , medicine , endocrinology , biochemistry , reductase , in vitro , biology , cholesterol , pravastatin , enzyme
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.