Effects Of Simvastatin On Bone Mass And The Expression Level Of Some Factors In Tgf-β/bmps And Wnt/β-catenin Signal Pathways In Proliferation And Differentiation Of Bone Marrow Stromal Cells In Rats

Objective:To investigate the effects of simvastatin on bone mass and the expression level of some factors in TGF-β/BMPs and Wnt/β-catenin signal pathways in proliferation and differentiation of bone marrow stromal cells in rats.Methods:Thirty-two 5-week-old female Sprague-Dawley rats were randomized into four groups of eight animals each: G1, administered daily with 20 mg/kg of simvastatin by gavage for six weeks; G2, control group with Vehicle for six weeks; G3, administered daily with 20 mg/kg of simvastatin by gavage for nine weeks; G4, control group with Vehicle for nine weeks.Double labeling was performed with subcutaneous injections of tetracylcin 10 days before sacrifice and of calcein 4 days before sacrifice. All animals were sacrificed one day after the final administration. The left femora were removed for the measurement of bone histomorphometry and bone mineral density (BMD). BMSCs were derived from the right femora and tibiae. The cells were differentiated into osteoblast. Cell Counting Kit-8 (CCK-8) was used to assay the proliferation of BMSCs. Alkaline phosphatase (ALP) activity, ALP staining were performed at the 16th d and von Kossa staining at the 28th d. Real-time RT-PCR was used to evaluate the expression level of mRNA of Smad1, Smad2, Smad7, LRP-5, Axin-2,β-catenin at the 21th d. Results:After being administrated with simvastatin for 6 and 9 weeks, the bone mass and bone mineral density (BMD) of rats had no significant change between administration groups and control groups. The expression level of mRNA of Smad1, Smad2, Smad7, LRP-5, Axin-2, β-catenin showed no significant change, so were the results of ALP activity, ALP staining, von Kossa staining and the proliferation of BMSCs.Conclusion:Administrated with simvastatin for six and nine weeks has no significant effects on bone mass and the expression level of some factors in TGF-β/BMPs and Wnt/β-catenin signal pathways in proliferation and differentiation of bone marrow stromal cells in rats.