title: [Effects of simvastatin on bone formation relative factors of trabecular bone and osteogenic differentiation of bone marrow mesenchymal stem cells in young rats].
abstract: OBJECTIVE
  Simvastatin has been reported to be effective on stimulation of bone formation. To investigate the effects of simvastatin on bone formation relative factors of proximal tibia trabecular bone and on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).
  
  
  METHODS
  Fourty 1-week-old male Sprague Dawley rats were divided randomly into 2 groups, 20 rats per group. Rats in experimental group received subcutaneous injection of simvastatin [(5 mg/(kg x d)], and the rats in control group received injection of normal saline at the same dose. The expressions of bone morphogenetic protein 2 (BMP-2), matrix metalloproteinase 13 (MMP-13), and vascular endothelial growth factor (VEGF) of trabecular bone were analyzed in the tibia by immunohistochemical staining at 1 and 3 weeks after injection. BMSCs from the rat femur at 1 and 3 weeks after injection were cultured under condition of osteogenic induction. ALP staining was performed on the 14th day after culture; real-time fluorescent quantitative PCR was used to detect the mRNA expressions of BMP-2, Runx2, Osterix, Msx2, Dlx3, and Dlx5 on the 21st day after culture; and von Kossa staining was performed on the 28th day after culture.
  
  
  RESULTS
  There was no significant difference in the expressions of BMP-2, MMP-13, and VEGF between the experimental group and control group at 1 and 3 weeks after injection (P > 0.05). There was no significant difference in the percentages of ALP positively-stained cells between the experimental group and the control group on the 14th day after culture (P > 0.05). The mRNA expressions of BMP-2, Runx2, Osterix, Msx2, D1x3, and Dlx5 in osteogenic differentiation-induced BMSCs had also no significant difference between the experimental group and the control group at 1 and 3 weeks after culture (P > 0.05). No significant difference in biomineralization was found between the experimental group and control group at 1 and 3 weeks after culture (P > 0.05).
  
  
  CONCLUSIONS
  Subcutaneous injection of simvastatin [(5 mg/(kg x d)] for 1 or 3 weeks can affect neither the expressions of bone formation relative factors of proximal tibia trabecular bone nor the osteogenic differentiation of the BMSCs.
authors.affiliation: Department of Orthopedics, Affiliated Hospital of North China Coal Medical University, Tangshan Hebei, 063000, PR China. zhliu130@sohu.com
authors.forename: Liu
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Liu
authors.forename: Faming
authors.initials: F
authors.lastname: Tian
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Dacheng
authors.initials: D
authors.lastname: Han
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D019821:Simvastatin; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat