Abstract:

Objective    To investigate whether simvastatin(SIM) can promote differentiation of rat bone marrow mesenchymal stem cells(BMSCs ) to osteablasts by regulating TGF-β1/Smad signaling pathways.  Methods   Rat BMSCs were recovered, cultured and further induced to differentiate into osteoblasts. Different concentration of SIM（10-8 mol/L、10-7 mol/L、10-6 mol/L） was added in the experimental group, and the control group no drug intervention was given in the control group. 7 days after ostrogenic solution was added, alkaline phosphatase staining was used to observe the expression level of bone formation, Alizarin Red staining was used to observe calcification level,and Western blot was used to determine the expression of of TGF-β1,Smad2 and Smad3.   Results   Treatment with SIM at concentrations of 10-8 mol/L to 10-6 mol/L for 7 d  significantly increased the activity of ALP, and SIM at concentration of 10-7 mol/L produced the maximum effect. Exposure of the cells to SIM at concentration of 10-8 mol/L～10-6 mol/L for 21 d significantly increased mineralized nodules. Exposure of the cells to SIM at concentrations of 10-8～10-6 mol/L for 7 d markedly increased the expression of TGF-β1, Smad2 and Smad3.   Conclusion   SIM could promote the osteogenic differentiation of BMSCs，in which process the changes of the mRNA expression levels inTGF-β1/Smad signaling pathway might participate.

Key words: Simvastatin, Bone marrow mesenchymal stem cells, Osteoblasts, TGF-β1