[Effect of simvastatin on bone morphogenetic protein-2 expression and alkaline phosphatase activity of bone marrow stromal cell].
OBJECTIVE
To study the effect of simvastatin on the expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphates (ALP) activity in the primary cultured bone marrow stromal cells, and to elucidate the mechanism of the anabolic osteogenetic effect of simvastatin.


METHODS
Bone marrow stromal cells in femur and tibia of adult mouse were cultured in vitro. after treated with different concentrations of simvastatin (0, 0.1, 0.2, 0.5 and 1.0 mumol/L) or recombinant human BMP-2 for 72 hours, ALP activity of bone marrow stromal cells was determined. BMP-2 expression of bone marrow stromal cells was analyzed by using immunocytochemistry and Western blotting.


RESULTS
After treated with simvastatin for 72 hours, BMP-2 expression increased, while little BMP-2 expression could be observed in the control group. ALP activity also increased in a dose-dependent manner; t-test showed that ALP activity in the group which concentrations of simvastatin were 0.5 mumol/L (t = 2.35, P = 0.041), 1.0 mumol/L (t = 2.348, P = 0.041) had significant difference when compared with control group.


CONCLUSIONS
Simvastatin lead to high expression of BMP-2 in bone marrow stromal cells, via the increased auto- or para-crine of BMP-2, and ALP activity increased. These may be parts of the mechanism on the anabolic osteogenetic effect of simvastatin.
Song
Chun-li
CL
Department of Orthopedic Surgery, Third Hospital of Peking University, Beijing, P. R. China 100038. songchunli@263.net
Dang
Geng-ting
GT
Guo
Zhao-qing
ZQ
D000469:Alkaline Phosphatase / Q000096:biosynthesis*; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology*; D017154:Stromal Cells / Q000378:metabolism*; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D019821:Simvastatin; D000469:Alkaline Phosphatase