Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells.
To clarify the mechanism of the stimulatory effect of statins on bone formation, we investigated the effect of simvastatin, a widely used statin, on osteoblastic and adipocytic differentiation in primary cultured mouse bone marrow stromal cells (BMSCs). Simvastatin treatment enhanced the expression level of mRNA for osteocalcin and protein for osteocalcin and osteopontin, and increased alkaline phosphatase activity significantly (p<0.05). After BMSCs were exposed to an adipocyte differentiation agonist, Oil Red O staining, fluorescence activated cell sorting, and decreased expression level of lipoprotein lipase mRNA showed that treatment with simvastatin significantly inhibits adipocytic differentiation compared to controls that did not receive simvastatin (p<0.05). Lastly, we found that simvastatin induces high expression of BMP(2) in BMSCs. These observations suggested that simvastatin acts on BMSCs to enhance osteoblastic differentiation and inhibits adipocytic differentiation; this effect is at least partially mediated by inducing BMP(2) expression in BMSCs.
Song
Chunli
C
Department of Orthopedics, Peking University Third Hospital, Beijing, PR China.
Guo
Zhaoqing
Z
Ma
Qingjun
Q
Chen
Zhongqiang
Z
Liu
Zhongjun
Z
Jia
Hongti
H
Dang
Gengting
G
D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D019821:Simvastatin / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019821:Simvastatin