2003
DOI: 10.1016/s0006-291x(03)01408-6
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Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells

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Cited by 170 publications
(142 citation statements)
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“…Statins stimulate increased expression of the BMP-2 gene in osteoblasts, and simvastatin has been suggested to activate the protein kinase pathway and resist the inhibitory action of TNF-α on BMP-2-induced osteoblast differentiation by regulating Smad signaling and Ras/Rho mitosis (25,26). Statins are associated with a variety of other activities including induction of osteoblast differentiation (27), resistance of the inhibitory effects on osteoblast growth and enhancement of osteoclast activity induced by IL-1, IL-6, TNF-α and other inflammatory factors (28), inhibition of matrix metalloproteinase activity (29), upregulation of vascular endothelial growth factor (VEGF) (30), enhanced activity of endothelial nitric oxide synthase (eNOS) (31) and inhibition of differentiation of adipose cells from multipotential stem cells (32).…”
Section: Discussionmentioning
confidence: 99%
“…Statins stimulate increased expression of the BMP-2 gene in osteoblasts, and simvastatin has been suggested to activate the protein kinase pathway and resist the inhibitory action of TNF-α on BMP-2-induced osteoblast differentiation by regulating Smad signaling and Ras/Rho mitosis (25,26). Statins are associated with a variety of other activities including induction of osteoblast differentiation (27), resistance of the inhibitory effects on osteoblast growth and enhancement of osteoclast activity induced by IL-1, IL-6, TNF-α and other inflammatory factors (28), inhibition of matrix metalloproteinase activity (29), upregulation of vascular endothelial growth factor (VEGF) (30), enhanced activity of endothelial nitric oxide synthase (eNOS) (31) and inhibition of differentiation of adipose cells from multipotential stem cells (32).…”
Section: Discussionmentioning
confidence: 99%
“…Since locally applied statins were found to be potent stimulators of bone formation 5) , the possibility of using these compounds as practical bone anabolic agents has been postulated. Song et al reported that statins promote osteoblast differentiation and expression of BMPs in mouse bone marrow stromal cells 6) .…”
Section: Introductionmentioning
confidence: 99%
“…Previous in vitro studies have indicated that statins in the dose range of 0.01-5 µM increase expression of osteogenic marker genes, such as RUNX-2, BMP-2, osteocalcin, osteopontin, and alkaline phosphatase, in cultured osteoblastic cells and bone marrow-derived cells. [9][10][11][12][13][14][15] In this study, the amount of simvastatin released daily was within the concentrations range of 0.02-0.53 µg/day (0.1-5 µM/day), which significantly stimulated osteogenic gene expression of RUNX-2, BMP-2, alkaline phosphatase, and osteocalcin ( Figure 3A-D) and final mineralization ( Figure 3E) in cultured D1 cells. This result indicates that this newly developed SIM/PLGA/HAp system releases a nontoxic therapeutic dose of simvastatin for osteogenesis in bone marrow stromal cells.…”
Section: Discussionmentioning
confidence: 53%
“…[10][11][12][13][14][15] Previous in vivo studies showed that oral administration of a high dose of simvastatin (20 mg/kg/day) enhances trabecular bone volume in ovariectomized rats. 9, 16 Skoglund et al also reported that systemic administration of an extremely high dose of simvastatin (120 mg/kg/day) in mice increases bone healing.…”
mentioning
confidence: 99%