コレステロール合成阻害剤(スタチン)による骨芽細胞分化制御に関する研究

概要

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The cholesterol-lowering drugs statins, including simvastatin, cerivastatin and atorvastatin, are pro-drug of a potent 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors and inhibit cholesterol synthesis in humans and animals. Simvastatin at 10^<-7> M markedly increased mRNA expression of BMP-2, VEGF, alkaline phosphatase, type I collagen, bone sialoprotein, and osteocalcin (OCN) in MC3T3-E1 cells, and clearly suppressed gene expression of matrix metalloproteinase (MMP)-1 and MMP-13. Extracellular accumulation of proteins such as VEGF, OCN, collagenase-digestive proteins, and noncollagenous proteins, was elevated in MC3T3-E1 cells treated with 10^<-7> M simvastatin, and 10^<-8> M cerivastatin. MC3T3-E1 cells stimulated mineralization by treatment of statins, and pretreating these cells with mevalonate, or geranylgeranyl pyrophosphate, mevalonate metabolite, abolished statin induced mineralization. The results indicated that statins stimulate osteoblast differentiation in vitro, and suggest that statins will become useful drugs for the treatment of osteoporosis in the future.
2004-03-31