gp130 activation by soluble interleukin-6 receptor/interleukin-6 enhances osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells
gp130 activation by soluble interleukin-6 receptor/interleukin-6 enhances osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells
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DOI：
10.1006/excr.2002.5627
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发表时间：
2002-10-15
影响因子：
3.7
通讯作者：
Minguell, JJ
中科院分区：
文献类型：
--
作者：
Erices, A;Conget, P;Minguell, JJ
白细胞介素-6 （IL-6）促进骨祖细胞的骨分化；然而，目前尚不清楚这种细胞因子是否会影响骨髓内骨祖细胞的分化。为了解决这一问题，我们制备了具有细胞表面表型和多电位特性的人骨髓间充质干细胞（MSCs）。我们观察到，在IL-6存在的情况下，MSCs不能分化成成骨谱系，这可以通过诱导碱性磷酸酶活性（骨分化的早期标志）的失败来证明。IL-6缺乏作用与观察到的MSCs不表达膜结合或可溶性IL-6受体（sIL-6R）有关。与其他il - 6r阴性细胞不同，单独添加sIL-6R或sIL-6R/IL-6复合物不能逆转IL-6的无能。然而，在地塞米松使MSC成骨后，sIL-6R或sIL-6R/ IL-6复合物增强了碱性磷酸酶活性。事实证明，sIL-6R或sIL-6R/IL-6的作用依赖于gp130的可用性，gp130由MSCs表达，涉及stat-3磷酸化。这些数据表明，IL-6R缺乏可能代表了骨髓间充质祖细胞逃避IL-6成骨作用的一种保护机制，IL-6是由MSC本身以及其他骨髓基质细胞产生的。(C) 2002 Elsevier Science （USA）。
Interleukin-6 (IL-6) promotes osteodifferentiation in bone-located progenitors; however, it is not known whether this cytokine affects the differentiation of bone marrow-located osteoprogenitors. To address this issue, we prepared human bone marrow-derived mesenchymal stem cells (MSCs), which were characterized by a cell surface phenotype and multipotential nature. It was observed that in the presence of IL-6, MSCs were not differentiated into the osteogenic lineage, as evidenced by a failure to induce alkaline phosphatase activity, an earlier marker of osteodifferentiation. The lack of effect of IL-6 correlates with the observation that MSCs do not express a membrane-bound or soluble IL-6 receptor (sIL-6R). The incompetence of IL-6 was not reversed by the addition of sIL-6R alone or the sIL-6R/IL-6 complex, as it occurs in other IL-6R-negative cells. However, after MSC osteocommittment by dexamethasone, sIL-6R or the sIL-6R/ IL-6 complex enhanced alkaline phosphatase activity. The effect of sIL-6R or sIL-6R/IL-6 proved to be dependent on gp130 availability, which is expressed by MSCs, and involves stat-3 phosphorylation. These data suggest that IL-6R deficiency may represent for bone marrow-located mesenchymal progenitors a sort of protective mechanism to escape the osteogenic effect of IL-6, which is produced by the MSC itself as well as by other marrow stromal cells. (C) 2002 Elsevier Science (USA).