Regulation of Mesenchymal Stem Cell Osteogenic Differentiation by Glucocorticoid-induced Leucine Zipper (GILZ)*
Regulation of Mesenchymal Stem Cell Osteogenic Differentiation by Glucocorticoid-induced Leucine Zipper (GILZ)*
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DOI：
10.1074/jbc.m704147200
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发表时间：
2008-02
影响因子：
4.8
通讯作者：
Weixi Zhang;Nianlan Yang;Xinglin Shi
中科院分区：
文献类型：
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作者：
Weixi Zhang;Nianlan Yang;Xinglin Shi
间充质干细胞（Mesenchymal stem cells，MSCs）可以分化为多种细胞系，包括成骨细胞和脂肪细胞。我们以前报道过糖皮质激素诱导的亮氨酸拉链（GILZ）抑制过氧化物酶体增殖物激活受体γ 2（Pparγ2）的表达并阻断脂肪细胞分化。在这里，我们表明，在小鼠骨髓间充质干细胞，而不是MC 3 T3-E1成骨细胞中过表达GILZ，增加碱性磷酸酶活性，并增强矿化骨结节的形成，而敲低Gilz降低MSC成骨分化能力。与这些观察结果一致，实时逆转录PCR分析表明，无论是基础和分化诱导的成绩单的谱系承诺基因Runx 2/Cbfa 1，以及成骨细胞分化标志物基因，包括碱性磷酸酶，I型胶原，骨钙素，都增加了GILZ表达细胞。相反，在成骨和成脂条件下，GILZ表达细胞中成脂Pparγ2和C/ebpα的mRNA水平显著降低。总之，我们的研究结果表明，GILZ作为MSC的调节剂发挥作用，并且GILZ的过表达将MSC的成骨和成脂分化之间的平衡向成骨途径转移。这些数据表明，GILZ可能对代谢性骨病（如骨折修复）的干细胞治疗具有治疗价值。
Mesenchymal stem cells (MSCs) can differentiate into multiple cell lineages, including osteoblasts and adipocytes. We reported previously that glucocorticoid-induced leucine zipper (GILZ) inhibits peroxisome proliferator-activated receptor γ-2 (Pparγ2) expression and blocks adipocyte differentiation. Here we show that overexpression of GILZ in mouse MSCs, but not MC3T3-E1 osteoblasts, increases alkaline phosphatase activity and enhances mineralized bone nodule formation, whereas knockdown of Gilz reduces MSC osteogenic differentiation capacity. Consistent with these observations, real-time reverse transcription-PCR analysis showed that both basal and differentiation-induced transcripts of the lineage commitment gene Runx2/Cbfa1, as well as osteoblast differentiation marker genes including alkaline phosphatase, type I collagen, and osteocalcin, were all increased in GILZ-expressing cells. In contrast, the mRNA levels of adipogenic Pparγ2 and C/ebpα were significantly reduced in GILZ-expressing cells under both osteogenic and adipogenic conditions. Together, our results demonstrate that GILZ functions as a modulator of MSCs and that overexpression of GILZ shifts the balance between osteogenic and adipogenic differentiation of MSCs toward the osteogenic pathway. These data suggest that GILZ may have therapeutic value for stem cell-based therapies of metabolic bone diseases, such as fracture repair.