CAJ | 학술논문

目的：探讨低密度脂蛋白( low density lipoprotein, LDL)对小鼠成骨细胞增殖分化以及低密度脂蛋白受体相关蛋白5(low density lipoprotein receptor-related protein 5, LRP5)、dickkopf-1(DKK1)基因表达的影响,同时用阿托伐他汀对上述影响加以干预以分析阿托伐他汀在LDL对成骨细胞影响中的可能干预机制。方法分别运用CCK8、ELISA方法和荧光定量PCR方法检测浓度为0.05、0.10、0.20 mg/ml的LDL在24、48、72 h对成骨细胞增殖、骨钙素表达以及LRP5、DKK1基因mRNA表达的影响,然后检测10-6 mol/L和10-5 mol/L的阿托伐他汀在LDL对成骨细胞作用最明显的浓度影响下上述指标的变化。结果在LDL浓度为0.20 mg/ml时对成骨细胞增殖、骨钙素表达以及LRP5、DKK1基因mRNA表达的影响最明显。在LDL浓度为0.20 mg/ml的影响下,10-6 mol/L和10-5 mol/L的阿托伐他汀在48 h和72 h均能使小鼠成骨细胞增殖的抑制作用减弱,并明显增加骨钙素的表达,同时上调 LRP5 mRNA 表达水平,显著下调DKK1 mRNA表达水平,差异有统计学意义(均P<0.05)。结论阿托伐他汀能使LDL对小鼠成骨细胞增殖和分化的抑制作用减弱,其机制可能与影响成骨细胞wnt信号通路中LRP5及其抑制剂DKK1基因表达有关。
목적：탐토저밀도지단백( low density lipoprotein, LDL)대소서성골세포증식분화이급저밀도지단백수체상관단백5(low density lipoprotein receptor-related protein 5, LRP5)、dickkopf-1(DKK1)기인표체적영향,동시용아탁벌타정대상술영향가이간예이분석아탁벌타정재LDL대성골세포영향중적가능간예궤제。방법분별운용CCK8、ELISA방법화형광정량PCR방법검측농도위0.05、0.10、0.20 mg/ml적LDL재24、48、72 h대성골세포증식、골개소표체이급LRP5、DKK1기인mRNA표체적영향,연후검측10-6 mol/L화10-5 mol/L적아탁벌타정재LDL대성골세포작용최명현적농도영향하상술지표적변화。결과재LDL농도위0.20 mg/ml시대성골세포증식、골개소표체이급LRP5、DKK1기인mRNA표체적영향최명현。재LDL농도위0.20 mg/ml적영향하,10-6 mol/L화10-5 mol/L적아탁벌타정재48 h화72 h균능사소서성골세포증식적억제작용감약,병명현증가골개소적표체,동시상조 LRP5 mRNA 표체수평,현저하조DKK1 mRNA표체수평,차이유통계학의의(균P<0.05)。결론아탁벌타정능사LDL대소서성골세포증식화분화적억제작용감약,기궤제가능여영향성골세포wnt신호통로중LRP5급기억제제DKK1기인표체유관。
Objective The aim of this study was to explore the effect of low density lipoprotein ( LDL) on the proliferation and differentiation of MC3T3-E1 osteoblasts, as well as the expression of low density lipoprotein receptor-related protein 5(LRP5) and dickkopf-1(DKK1) mRNA of MC3T3-E1 osteoblasts. The possible mechanisms of the treatment of atorvastatin on LDL expression in MC3T3-E1 osteoblasts were also investigated. Methods Proliferation, osteocalcin expression, LRP5, and expression of DKK1 mRNA of MC3T3-E1 with interaction of LDL at 0. 05, 0. 10, 0. 20 mg/ml levels after 24 h, 48 h, 72 h were detected by CCK8, ELISA, and fluorescence quantitative PCR. Furthermore, proliferation, osteocalcin expression, LRP5 and DKK1 mRNA of MC3T3-E1 after the treatment of atorvastatin of 10-6 mol/L and 10-5 mol/L were also be studied, respectively. Results The effect of LDL on proliferation, expression of osteocalcin and expression of LRP5 and DKK1 mRNA in MC3T3-E1 osteoblasts was the most obvious under LDL with 0. 20 mg/ml level. Under that level, atorvastatin (10-6 mol/L or 10-5 mol/L) was able to make the proliferation of MC3T3-E1 osteoblasts in 48 h and 72 h be decreased, while significantly caused upregulation of osteocalcin, LRP5 mRNA expression; and down regulated DKK1 mRNA expression ( all P<0. 05). Conclusions Atorvastatin can reduce the inhibitory effect of LDL on the proliferation and differentiation of osteoblasts. The mechanisms of atorvastatin on osteoblasts are possibly related to the osteoblast proliferation and expression of LRP5 mRNA and DKK1 mRNA of osteoblasts of wnt signal pathway.