辛伐他汀可刺激骨髓间充质干细胞的成骨分化

背景:辛伐他汀可显著刺激骨髓间充质干细胞成骨分化,但机制不明.近年研究证实p38 MAPK信号通路参与调控骨髓间充质干细胞向成骨细胞分化的过程.目的:观察p38丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路在辛伐他汀体外干预刺激骨髓间充质干细胞成骨分化中的作用....

Simvastatin stimulates osteogenic differentiation of bone marrow mesenchymal stem cells

BACKGROUND: Simvastatin can remarkably stimulate the osteogenic differentiation of bone marrow mesenchymal stem cells, but the mechanism is unknown. Recent studies have confirmed that p38 mitogen-activated protein kinase(MAPK) signaling pathway is involved in regulating the differentiation of bone marrow mesenchymal stem cells into osteoblasts. OBJECTIVE: To observe the role of p38 MAPK signaling pathway in simvastatin stimulated osteogenic differentiation of bone marrow mesenchymal stem cells. METHODS: Bone marrow mesenchymal stem cells from the femur and tibia of Sprague-Dawley rats were cultured in vitro, and the second generation of bone marrow mesenchymal stem cells was divided into three groups: control group, simvastatin group(10-7 mol/L simvastatin), and blocking agent group(10 μmol/L p38 MAPK signaling pathway specific blocker SB203580 30 minutes before adding simvastatin). Osteogenic differentiation was induced in DMEM complete medium containing 10 mmol/L β-glycerophosphate and 50 mg/L ascorbic acid. Alkaline phosphatase staining was performed at 6 days after intervention in each group. The expressions of p38 MAPK and phosphorylated p38 MAPK were detected by western blot assay at 6 and 12 days. The expression of osteocalcin and collagen type Ⅰ was detected by immunofluorescence and real-time fluorescent quantitative polymerase chain reaction at 12 days. The formation of calcium nodules was observed by alizarin red staining at 21 days. RESULTS AND CONCLUSION:(1) Alkaline phosphatase expression and matrix mineralization ability were significantly higher in the simvastatin group than those of control group, and significantly lower in the blocker group than those in the simvastatin group(P < 0.05).(2) The ratio of p38 MAPK in simvastatin group was significantly higher than that in control group(P < 0.05), and that in blocker group was significantly lower than that in simvastatin group(P < 0.05).(3) Simvastatin could promote the expression levels of osteocalcin and collagen type Ⅰ, while above expression levels in the blocker group were significantly lower than those in the simvastatin group(P < 0.05).(4) It is concluded that simvastatin could promote the differentiation of bone marrow mesenchymal stem cells into osteoblasts, which may be related to stimulate the phosphorylation of p38 MAPK, thereby enhancing the activity of this pathway.