Objective To observe the effects of 17β-E2 and Wnt/β-catenin signaling pathways on the expres-sion of matrix Gla protein (MGP) in osteosarcoma cells (MG63), to investigate the potential role and the possible mechanism of MGP in osteoporosis.Methods MG63 cells were intervened by 17β-E2 (10 -10 , 10 -8 , 10 -6 ) mol/L, the inhibitor of estrogen receptor ICI 10 -7 mol/L for 48 h.MG63 cells were intervened by 17β-E2 10 -8 mol/L, (Dickkopf1) DKK-1 200 ng/mL, 17β-E2 10 -8 mol/L +DKK 1 200 ng/mL for 48 h.MG63 cells were inter-vened by 17β-E2 10 -8 mol/L, Warfarin 10 -5 mol/mL, 17β-E2 10 -8 mol/L +warfarin 10 -5 mol/mL for 48 h, then total RNA and protein was extracted.Real-time quantitative ( RT-PCR) and Western blotting were used to de-tectMGP,β-catenin,Runx2,LRP5geneandproteinexpression.Results 17β-E2couldup-regulatetheex-pression of MGP, at the concentration of 10 -10 , 10 -8 , 10 -6 mol/L.MGP mRNA expression were 4.63-fold, 7.16-fold, 2.95-fold, and MGP protein expression was 1.17-fold, 1.58-fold, 1.28-fold, compared with the control (P<0.05).At the concentration of 10 -8 mol/L, the effects of the 17 β-E2 was more obvious.The modu-lating effect of MGP by 17β-E2 was blocked after (Faslodex) ICI was used (P<0.05).17β-E2 increased the ex-pression of mRNA and protein of Wnt-associated proteinβ-catenin and LRP5.The Wnt/β-catenin signaling pathway inhibitor, DKK-1 could block the upregulation effect of MGP by 17β-E2 significantly ( P<0.05 ) .Warfarin de-creased the expression of MGP and block the upregulation effect of β-catenin, LRP5, Runx2 by 17β-E2 significant-ly ( P<0.05) .Conclusion It is maybe the mechanism of osteoporosis that 17β-E2 modulated the expression of MGP through Wnt/β-catenin signaling pathways.%目的：观察17β-雌二醇（17β-E217β-estradiol）对骨肉瘤细胞（osteosarcoma MG 63）基质Gla蛋白（MGP Matrix GLA protein）表达的影响及Wnt／β-catenin信号通路在其中的作用，探讨MGP在骨质疏松症发病过程中的可能机制。方法17β-E210－10、10－8、10－6mol／L及雌激素受体抑制剂氟维司群（Faslodex简称ICI）10－7 mol／L， ICI 10－7 mol／L ＋17β-E210－8 mol／L干预MG63细胞48 h。用10－8 mol／L的17β-E2及200 ng／mL Wnt／β-catenin信号通路阻断剂Dickkopf1分泌蛋白-1（ DKK-1）干预MG63细胞48 h。用10－8 mol／L 17β-E2及MGP抑制剂华法林10μmol／L干预MG63细胞48 h。干预后的细胞提取蛋白及总RNA，后用荧光定量PCR及Westernblotting观察MGP、β-catenin、Runx2、LRP5蛋白及基因的表达。结果17β-E2能上调MGP的表达，10－10、10－8、10－6 mol／L 17β-E2干预后， MGP mRNA的表达是对照组的4.63、7.16、2.95倍（ P＜0.05）， MGP蛋白的表达分别是对照组的1.17、1.58、1.28倍（ P＜0.05），以10－8 mol／L 17β-E2的作用最明显。 ICI 能阻断17β-E2对MGP的上调作用，与单用17β-E2相比，差异有统计学意义（ P＜0.05）。17β-E2能增加Wnt／β-catenin经典信号通路中相关蛋白的表达，β-catenin及Runx2 mRNA及蛋白的表达与对照组相比，差异有统计学意义（ P＜0.05）。DKK-1则阻断17β-E2对MGP、β-catenin、 Runx2、 LRP5的上调作用，与对照组相比，差异有统计学意义（ P ＜0.05）。华法林可阻断17β-E2的作用，与对照组相比 MGP、β-catenin、Runx2、LRP5的表达均下调，差异有统计学意义（P＜0.05）。结论17β-E2调节成骨肉瘤细胞内Wnt／β-catenin信号通路同时也调节MGP表达，该作用可能是骨质疏松症发病的机制之一。
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