Mizuno Daiki, Agata Hideki, Furue Hiroki, Kimura Ayuko, Narita Yuji, Watanabe Nobukazu, Ishii Yumiko, Ueda Minoru, Tojo Arinobu, Kagami Hideaki
Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Growth Factors. 2010 Feb;28(1):34-43. doi: 10.3109/08977190903326362.
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.
尽管有大量报告描述了重组人骨形态发生蛋白-2（rhBMP-2）在体内的骨形成能力，但研究报告称其对人间充质干细胞（hMSCs）的作用有限。然而，这些差异的原因尚不清楚。本研究的目的是研究hMSCs对骨诱导信号的反应性，重点是rhBMP-2以及血清对该反应性的影响。分析了来自六个供体的人MSCs。当这些细胞用含地塞米松（Dex）的骨诱导培养基处理时，所有细胞系中的碱性磷酸酶（ALP）活性均增加。另一方面，含rhBMP-2的培养基未能增加ALP活性。当使用五种不同的血清与rhBMP-2一起进行培养和诱导时，其中两种血清中的ALP活性增加，而其他血清中则未增加。无论对rhBMP-2的反应性如何，几乎在所有组合中均诱导了BMP-2拮抗剂头蛋白（noggin）的表达。另一方面，卵泡抑素（follistatin）的表达根据血清和细胞系显示出显著差异。然而，该表达与对rhBMP-2的反应性无关。本研究结果表明，hMSCs对rhBMP-2的成骨反应有限但具有异质性，并且结果受血清选择的影响。这一事实在rhBMP-2成功有效的临床应用中应予以关注。
