ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential
ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential
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DOI：
10.1016/j.yexcr.2008.01.020
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发表时间：
2008-05-01
影响因子：
3.7
通讯作者：
Trigueros, Cesar
中科院分区：
文献类型：
--
作者：
Carcamo-Orive, Ivan;Tejados, Naiara;Trigueros, Cesar
人骨髓间充质干细胞（humanmesenchymalstemcells，hMSC）主要来源于成人骨髓，是研究干细胞自我更新和分化的重要模型。由于细胞外信号调节激酶（ERK）信号通路是细胞生长、分化和存活的主要贡献者，我们研究了该激酶在hMSC活性中的功能。通过RNA干扰去除ERK 2基因表达（但不去除ERK 1）显著降低了hMSC的增殖。这种减少是由于细胞周期蛋白D1表达的缺陷和随后在细胞周期的G 0/G1期的停滞。通过培养基补充生长因子（GF）如血小板衍生生长因子（PDGF）、碱性成纤维细胞生长因子（bFGF）或表皮生长因子（EGF）来增强hMSC生长。然而，这些补充剂不能挽救ERK 2敲低后观察到的缺陷，这表明这些GF用于增殖的共同信号传导途径。相反，ERK 1/2可能与由相同的GF诱导的趋化性信号传导分离。此外，即使在ERK 1或ERK 2蛋白不存在的情况下，hMSC也能够分化为脂肪细胞。我们的数据表明，hMSCs不需要细胞分裂进入成脂分化过程，表明这些细胞的克隆扩增不是一个关键步骤。然而，细胞-细胞接触似乎是能够分化成成熟脂肪细胞的基本要求。(C)2008年爱思唯尔公司All rights reserved.
Human Mesenchymal Stem Cells (hMSC), derived mainly from adult bone marrow, are valuable models for the study of processes involved in stem cell self-renewal and differentiation. As the Extracellular signal-Regulated Kinase (ERK) signalling pathway is a major contributor to cellular growth, differentiation and survival, we have studied the functions of this kinase in hMSC activity. Ablation of ERK2 gene expression (but not ERK1) by RNA interference significantly reduced proliferation of hMSC. This reduction was due to a defect in Cyclin D1 expression and subsequent arrest in the G0/G1 phase of the cell cycle. hMSC growth is enhanced through culture medium supplementation with growth factors (GFs) such as Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF) or Epidermal Growth Factor (EGF). However, these supplements could not rescue the defect observed after ERK2 knockdown, suggesting a common signalling pathway used by these GFs for proliferation. In contrast, ERK1/2 may be dissociated from chemotactic signalling induced by the same GFs. Additionally, hMSCs were capable of differentiating into adipocytes even in the absence of either ERK1 or ERK2 proteins. Our data show that hMSCs do not require cell division to enter the adipogenic differentiation process, indicating that clonal amplification of these cells is not a critical step. However, cell-cell contact seems to be an essential requirement to be able to differentiate into mature adipocytes. (C) 2008 Elsevier Inc. All rights reserved.