Limited but heterogeneous osteogenic response of human bone marrow mesenchymal stem cells to bone morphogenetic protein-2 and serum
Limited but heterogeneous osteogenic response of human bone marrow mesenchymal stem cells to bone morphogenetic protein-2 and serum
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DOI：
10.3109/08977190903326362
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发表时间：
2010-02-01
期刊：
影响因子：
1.8
通讯作者：
Kagami, Hideaki
中科院分区：
文献类型：
--
作者：
Mizuno, Daiki;Agata, Hideki;Kagami, Hideaki
尽管有大量报道描述了重组人骨形态发生蛋白-2(rhBMP-2)在体内的成骨能力，但对人骨髓间充质干细胞(HMSCs)的作用有限。然而，造成这些差异的原因并未得到很好的理解。本研究的目的是研究人骨髓间充质干细胞对骨诱导信号的反应性，重点是重组人骨形态发生蛋白-2以及血清对这种反应性的影响。对6例供者的骨髓间充质干细胞进行了分析。用含地塞米松(Dex)的成骨诱导剂处理后，所有细胞系的碱性磷酸酶(ALP)活性均升高。另一方面，含rhBMP-2的培养液不能提高碱性磷酸酶的活性。用5种不同的血清进行培养和诱导时，其中2种血清的ALP活性升高，其余的则无明显变化。BMP-2拮抗剂noggin在几乎所有的组合中都被诱导表达，而与对rhBMP-2的反应性无关。另一方面，卵泡抑素的表达因血清和细胞系的不同而有显著差异。然而，该表达与对rhBMP-2的反应性无关。这项研究的结果表明，hMSCs对重组人骨形态发生蛋白-2的成骨反应有限但不同，而且结果受到血清选择的影响。这一事实对于成功和有效地应用重组人骨形态发生蛋白-2的临床应用值得关注。
Although there are numerous reports describing the in vivo bone forming capability of recombinant human bone morphogenetic proteins-2 (rhBMP-2), studies have reported limited effects on human mesenchymal stem cells (hMSCs). However, the reasons for these discrepancies are not well understood. The aim of this study was to investigate the responsiveness of hMSCs to osteoinductive signals, focusing on rhBMP-2 and the effect of serum on that responsiveness. Human MSCs from six donors were analysed. When those cells were treated with osteoinduction medium including dexamethasone (Dex), alkaline phosphatase (ALP) activities increased in all cell lines. On the other hand, rhBMP-2-containing medium failed to increase ALP activity. When five different sera were used for cultivation and induction with rhBMP-2, ALP activities increased in two of them, but not in the others. The expression of BMP-2 antagonist noggin was induced in almost all combinations regardless of the responsiveness to rhBMP-2. On the other hand, the expression of follistatin showed significant variations depending on the serum and cell line. However, the expression did not correlate with the responsiveness to rhBMP-2. The results from this study showed limited but heterogeneous osteogenic response of hMSCs to rhBMP-2 and that the results are affected by the choice of serum. This fact should be concerned for the successful and effective clinical application of rhBMP-2.