The Effects And Mechanisms Of Simvastatin On Human Dental Pulp Cells In Vitro

Objective:To investigate the effects and mechanisms of simvastatin on human dental pulpcells（hDPCs） in vitro.Methods:1. hDPCs were cultured according to the method of modified tissue culture.Thendifferent concentrations of simvastatin were added into each group of hDPCs until theultimately concentrations were10^-2,10^-2,10-1and1μmol/mL respectively while thegroup without simvastatin as control group. The suitable concentration wasdetermined and further to subdivided.2. The former concentrations of simvastatin,which were0.5×10^-2,10^-2,1.5×10^-2and5×10^-2μmol/mL,were further subdivided to add into the hDPCs and lipopoly-saccharides （LPS）-induced hDPCs.The optimal suitable simvastatin concentration wasfound out.3. After simvastatin irradiation,the changes of vascular endothelial growthfactor （VEGF） were examined in the level of genes and proteins.4. The expression of bone morphogenetic protein^-2(BMP^-2) mRNA of hDPCsand LPS-induced hDPCs were measured at different time points under simvastatinirradiation.The alkaline phosphatase （ALP） staining were observed in the four groups.Results:1. Low concentration(10^-2μmol/mL) simvastatin enhanced hDPCs’proliferation,however, high concentration（1μmol/mL） simvastatin inhibited hDPCs’ proliferation.2.0.5×10^-2,10^-2,1.5×10^-2and5×10^-2μmol/mL of simvastatin were added tohDPCs and LPS-induced hDPCs.We found that10^-2μmol/mL enhanced hDPCs’pro-liferation but inhibited the proliferation of LPS-induced hDPCs.3. Simvastatin significantly increased hDPCs’ VEGF protein levels at3days andat5days. With LPS irradiation,the VEGF protein levels increased significantly on hDPCs at3days and at5days;but simvastatin inhibited the LPS-induced hDPCs’VEGF protein and gene levels,respectively.4. Simvastatin and LPS enhanced BMP^-2 mRNA levels of hDPCs,respectively.Then simvastatin inhabited the expression of BMP^-2 mRNA.5. The ALP staining on hDPCs without any stimulation was lighter than withsimvastatin,but darker than with LPS.Simvastatin suppressed the ALP activity of LPS-induced hDPCs.Conclusion：1. Simvastatin in10^-2μmol/mL enhanced hDPCs’proliferation and inhibited theproliferation of LPS-induced hDPCs.2. The optimal concentration of simvastatin increased VEGF protein and mRNAlevels of hDPCs,but inhaibited that of LPS-induced hDPCs.3. The suitable concentration of simvastatin enhanced BMP^-2 mRNA of hDPCs,and enhanced ALP activity.4. On LPS-induced hDPCs,the best concentration of simvasatin increasedBMP^-2 expression,but inhibited ALP activity.