Effect of simvastatin on osteoblastic differentiation of bone marrow stromal cells in rats

AIM: To study the effect on osteoblastic differentiation and proliferation of bone marrow stromal cells in vitro by administration of simvastatin in vivo and to elucidate the mechanism of the anabolic osteogenetic effect of simvastatin. METHODS: Thirty 3-month-old virgin female SD rats,weighting 250-300 g were randomly divided into 3 groups: Group 1,control,10 rats; Group 2,given simvastatin 10 mg/(kg·d),10 rats; Group 3,given simvastatin 20 mg/(kg·d),10 rats. All of the animals were given the agents through gastric tube for 28 d. At 29th day all the rats were sacrificed. Bone marrow stromal cells in femur and tibia were cultured in vitro. After treated with same condition for 14 d ALP activity of bone marrow stromal cells in supernatant was determined. The mRNA level of cbfa1 was detected by RT-PCR,and cbfa1 protein expression was analyzed by Western blot. Cell count kit (CCK-8) was used to examine the cell proliferation. RESULTS: After the rats were adminis- trated with different-dose simvastatin in vivo for 28 d,and then the bone marrow stromal cells were cultured for 14 d in vitro,the level of cbfa1 mRNA was increased,and the expression of cbfa1 protein also increased in a dose-dependent manner,and supernatant ALP activity increased in a dose-dependent manner. T-test showed that the proliferation of bone marrow stromal cells in Group 2 had significant difference,but no significant difference in Group 3,when compared with control group. CONCLUSION: Simvastatin leads to the high expression of cbfa1 in bone marrow stromal cells and increased ALP activity,which may be parts of the mechanisms underlying the anabolic osteogenetic effect of simvastatin.