【摘要】 [目的]研究辛伐他汀(simvastatin,SIM)促进大鼠骨髓基质干细胞(bone marrow stromal cells,BMSCs)向成骨细胞分化的作用机制。[方法]取4周雌性SD大鼠双侧股骨、胫骨骨髓细胞进行体外成骨诱导培养,并于第一次传代后(d8)加入浓度为10-7mol/LSIM(给药组,SIM组)或等量溶剂培养(对照组,N组),d16行碱性磷酸酶(ALP)染色,d28行vonKossa染色观察细胞外基质矿化,并采用realtime RT-PCR法于上述两个时间点检测b-catenin、BMP-2、Smad1、ALP、OCN、mRNA的表达。[结果]①辛伐他汀可促进成骨诱导分化大鼠BMSCs的ALP表达及细胞外基质的矿化能力。②mRNA表达水平:d16SIM组ALP的表达显著高于N组;d28SIM组BMP-2、Smad1、OCN表达水平均明显高于N组,b-catenin的表达显著低于N组(P﹤0.05)。[结论]辛伐他汀可促进大鼠BMSCs向成骨细胞分化,其作用机制可能与调节TGFβ/BMP、WNT信号途径相关基因的表达水平有关。更多还原

【Abstract】 [Objective] To investigate the stimulating effect of simvastatin on osteogenic differentiation of bone marrow stromal sells (BMSCs) of SD rats. [Methods] BMSCs derived from the tibia and femur of 4-week old female SD rats were cul- tured in vitro under osteoblastic-induced differentiation since the first subculture (8th day) and divided into 2 groups: control group (N), SIM treated group (SIM) .The cells of 1st subculture in SIM group were treated with SIM (10-7mol / L), cells in group N were treated with vehicle as control. Alkaline phosphatase (ALP) staining was applied at the 16th day and von Kossa staining was performed at 28th day to assess the osteoblastic differentiation and mineralization.Real time RT-PCR was performed to evaluate the expressions of b-catenin, BMP-2, Smad1, ALP, OCN mRNA at the two time points. [Results] ① SIM increased the expression of ALP and promoted the matrix mineralization. ② mRNA expression: At 16th day, the expression of ALP increased significantly in SIM group compared to N group; at 28th day, expression of BMP-2, Smad1, OCN in SIM group were significantly higher and b-catenin was significantly lower than those of group N (P﹤0.05). [Conclusion] SIM could promote the osteogenic differentiation of BMSCs, changes of the mRNA expression levels in some components of TGFβ / BMP and WNT signaling pathway might participate in this progress.更多还原