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首页> 外文期刊>Journal of Molecular Histology >Cell cycle related modulations in Runx2 protein levels are independent of lymphocyte enhancer-binding factor 1 (Lef1) in proliferating osteoblasts
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Cell cycle related modulations in Runx2 protein levels are independent of lymphocyte enhancer-binding factor 1 (Lef1) in proliferating osteoblasts

机译：Runx2蛋白水平中与细胞周期相关的调节独立于增殖成骨细胞中的淋巴细胞增强因子结合因子1（Lef1）

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摘要

Runt-related transcription factor Runx2 regulates osteogenic phenotype commitment and attenuates osteoblast growth. Runx2 levels are cell cycle regulated and maximal in the G1 phase of proliferating osteoblasts and during quiescence. The Wnt/Lrp5-Frizzled/β-catenin/Lef-Tcf signaling cascade also controls progression along the osteogenic lineage with a net anabolic effect that promotes bone formation. However, Lef1 opposes the osteoblast maturation promoting activity of Runx2. Here we examined whether Lef1 controls Runx2 expression during the cell cycle or onset of quiescence in osteoblasts. We inhibited Lef1 expression using short hairpin (sh) RNA interference in stably transfected MC3T3-E1 cells. In asynchronously growing osteoblasts, expression of Lef1 shRNA diminishes Lef1 protein levels, but does not affect Runx2 levels. Cells arrested in different cell cycle stages using mimosine (late G1), hydroxyurea or aphidicolin (S phase) or nocodazole (mitosis) exhibit expected reductions in Runx2 protein levels despite reductions in Lef1. Serum deprived MC3T3-E1 cells normally upregulate Runx2 protein regardless of Lef1 deficiency, although loss of Lef1 reduces cyclin A and increases cyclin D1 expression upon serum withdrawal. Thus, Runx2 protein levels during the cell cycle and onset of quiescence are regulated independently of Lef1, one of the major transcriptional inducers of Wnt signaling in proliferating cells.
机译：矮子相关转录因子Runx2调节成骨细胞表型，并减弱成骨细胞的生长。 Runx2的水平受细胞周期调节，在成骨细胞的G1期和静止期达到最大值。 Wnt / Lrp5-Frizzled /β-catenin/ Lef-Tcf信号级联反应还控制着成骨谱系的进展，具有促进骨形成的合成代谢作用。但是，Lef1反对Runx2的成骨细胞成熟促进活性。在这里，我们检查了Lef1是否在细胞周期或成骨细胞静止期开始时控制Runx2表达。我们在稳定转染的MC3T3-E1细胞中使用短发夹（sh）RNA干扰抑制Lef1表达。在异步生长的成骨细胞中，Lef1 shRNA的表达减少了Lef1蛋白的水平，但不影响Runx2的水平。尽管使用了Lef1，但使用含羞草（G1晚期），羟基脲或蚜虫碱（S期）或诺考达唑（有丝分裂）在不同细胞周期阶段停滞的细胞仍显示出Runx2蛋白水平的预期降低。尽管Lef1缺失，血清缺失的MC3T3-E1细胞通常会上调Runx2蛋白，尽管Lef1的丢失会降低血清中的细胞周期蛋白A并增加细胞周期蛋白D1的表达。因此，在细胞周期和静止期开始期间Runx2蛋白水平独立于Lef1调控，Lef1是增殖细胞中Wnt信号转导的主要转录诱导因子之一。

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  • 来源
    《Journal of Molecular Histology》 |2007年第5期|501-506|共6页
  • 作者

    Mario Galindo; Rachel A. Kahler; Nadiya M. Teplyuk; Janet L. Stein; Jane B. Lian; Gary S. Stein; Jennifer J. Westendorf; Andre J. van Wijnen;

  • 作者单位

    Department of Cell Biology and Cancer Center University of Massachusetts Medical School 55 Lake Avenue North Worcester MA 01655 USA;

    Departments of Orthopedic Surgery and Molecular Biology ampamp Biochemistry Mayo Clinic Rochester MN 55905 USA;

    Department of Cell Biology and Cancer Center University of Massachusetts Medical School 55 Lake Avenue North Worcester MA 01655 USA;

    Department of Cell Biology and Cancer Center University of Massachusetts Medical School 55 Lake Avenue North Worcester MA 01655 USA;

    Department of Cell Biology and Cancer Center University of Massachusetts Medical School 55 Lake Avenue North Worcester MA 01655 USA;

    Department of Cell Biology and Cancer Center University of Massachusetts Medical School 55 Lake Avenue North Worcester MA 01655 USA;

    Departments of Orthopedic Surgery and Molecular Biology ampamp Biochemistry Mayo Clinic Rochester MN 55905 USA;

    Department of Cell Biology and Cancer Center University of Massachusetts Medical School 55 Lake Avenue North Worcester MA 01655 USA;

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  • 正文语种 eng
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  • 关键词

    Runx2; Wnt signaling Lef1; Cell cycle; Aphidicolin; Mimosine; Nocodazole;

    机译：Runx2;Wnt信号传导Lef1;细胞周期;蚜虫碱;含羞草碱;诺考达唑;

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