Effect Of Simvastatin On Bone Marrow Mesenchymal Stem Cells Proliferation And Secretion Function Of

Objective: To investigate whether simvastatin of different concentrations have influences on the proliferation and paracrine functions of BMSCs in vitro and to explore its possible mechanism.Methods: BMSCs were isolated from Sprague–Dawley rats and expanded by whole bone marrow adherence culture method. Cells of 3 passage,which were at logarithmic phase,were used in experiment.BMSCs cultured in serum-free medium for 12 hours,then incubated with various concentrations of simvastatin for 24 hours. The influences of simvastatin on BMSCs'proliferation were assayed with CCK-8 assay, and their mRNA expressions of vascular endothelial growth factor(VEGF) and Hepatocyte growth factor(HGF) were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).Besides,Western-blot were used to investigate the pAkt and Akt expressions in BMSCs.Results: Simvastatin in a certain range of concentration (0.001umol/L-0.1umol/L) significantly increased proliferation and paracrine (VEGF and HGF) functions of BMSCs in vitro(P <0.01). Simvastatin at 0.01umol/L concentration reached the maximum effects on the proliferation and paracrine functions of BMSCs. While the concentration of simvastatin was further increased more than 0.01 umol/L, the improvement effects showed a tendency to decline. simvastatin at 1umol/L concentration had no significant effect on promoting proliferation of BMSCs but significantly increased the VEGF and HGF mRNA expression compared with the control group. Both pAKt expression and pAKt/AKt ratio in BMSCs were significantly higher than those in the control group after 0.01umol/L simvastatin treatment (P<0.01).Conclusion: Simvastatin in a definite concentration range could improve BMSCs' proliferation and paracrine capability, and the mechanism might be partially involved in the Akt pathway.