胰高血糖素样肽-1类似物对人成骨细胞Wnt信号通路相关基因表达的影响

Effect of glucagon like peptide-1 analogues on gene expression of Wnt signaling pathway-related factors in human osteoblasts

目的观察胰高血糖素样肽-1类似物(利拉鲁肽)对人成骨细胞增殖及Wnt信号通路相关因子mRNA的表达,探讨胰高血糖素样肽-1(GLP-1)与骨代谢的关系。方法向体外培养的人成骨细胞中分别加入浓度为0 mol/L、10-7 mol/L、10-8mol/L、10-9 mol/L的GLP-1类似物,24 h后采用Cell Counting Kit-8(CCK-8)比色法检测成骨细胞增殖率,实时荧光定量PCR(Real-time RT-PCR)法检测Wnt-3a、LRP-5、β-catenin mRNA的表达。结果 (1)GLP-1促进人成骨细胞增殖(P<0.05),随着给药浓度的增高,成骨细胞增殖率下降(P<0.05);(2)低浓度GLP-1(10-9mol/L)上调人成骨细胞中Wnt-3a、LRP-5、β-catenin mRNA的表达(P<0.05);高浓度GLP-1(10-7mol/L、10-8mol/L)下调人成骨细胞中Wnt-3a、LRP-5、β-catenin mRNA的表达(P<0.05)。结论 GLP-1促进人成骨细胞的增殖,低浓度时Wnt信号通路可能参与了该调控过程,高浓度抑制Wnt信号通路相关基因的表达。

Objective To investigate the effect of glucagon like peptide-1 （GLP-1） analogues （Liraglutide） on the proliferation of the human osteoblasts and the mRNA expression of Wnt signaling pathway-related factors, and to explore the relationship between GLP-1 and bone metabolism. Methods The different concentrations of GLP-1 analogues （0 mol/L, 10-7 mol/L, 10-8 moL/L, and 10-9 mol/L） were additioned to human osteoblast culture in vitro. Cell proliferation was determined using cell counting kit-8 （CCK-8） after 24 h. The mRNA expression levels of Wnt-3a, LRP-5, and β-catenin were detected using real time polymerase chain reaction （Real-time RT-PCR）. Results GLP-1 could promote the proliferation of human osteoblasts （P 〈 0. 05 ）, while the proliferation rate of osteoblasts declined along with the concentration increase （P 〈 0.05）. Low concentration of GLP-1 （ 10-9 mol/L） could up-regulate the mRNA expression levels of Wnt-3a, LRP-5, and [3-catenin in human osteoblasts （ P 〈 0. 05 ）. In contrast, high concentrations of GLP-1 （10-7 mol/L and 10-8 mol/L） could down-regulate the mRNA expression levels of Wnt-3a, LRP-5, and [3-catenin in human osteoblasts （P 〈 0.05）. Conclusion GLP-1 can promote the proliferation of human osteoblasts. When at low concentrations, Wnt signaling pathway may be involved in the regulatory process, while at high concentrations, it may inhibit the expression of Wnt signaling pathway-related genes.