EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation
EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation
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DOI：
10.1016/j.bone.2010.10.180
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发表时间：
2011-03-01
期刊：
影响因子：
4.1
通讯作者：
Gronthos, Stan
中科院分区：
文献类型：
--
作者：
Arthur, Agnieszka;Zannettino, Andrew;Gronthos, Stan
骨髓间充质干细胞（MSC）参与骨组织形成和造血调节。酪氨酸受体激酶的Eph/ephrin家族在维持神经、肠道和牙齿组织内的干细胞生态位中具有潜在的重要作用，最近已被证明在调节骨稳态中发挥作用。然而，EphB/ephrin-B分子在人MSC功能中的作用仍有待确定。在本研究中，EphB和ephrin-B分子在体外扩增的人骨髓间充质干细胞群体和人骨髓环钻样本中表达。为了阐明EphB/ephrin-B分子在MSC募集中的作用，我们进行了功能性扩散和迁移实验，结果表明，反向ephrin-B信号通路通过激活Src-、PI3Kinase-和jnk依赖性信号通路抑制MSC附着和扩散。相反，EphB2正向信号通过激活Src激酶和abl依赖的信号通路促进MSC迁移。此外，发现活化骨髓间充质干细胞表达的ephrin-B1和/或ephrin-B2分子可促进成骨分化，而活化ephrin-B1可促进软骨分化。这些观察结果表明，EphB/ephrin-B相互作用可能介导骨修复过程中MSC的募集、迁移和分化。(C) 2010爱思唯尔公司版权所有。
Bone marrow derived mesenchymal stem/stromal cells (MSC) contribute to skeletal tissue formation and the regulation of haematopoiesis. The Eph/ephrin family of receptor tyrosine kinases is potentially important in the maintenance of the stem cell niche within neural, intestinal and dental tissues and has recently been shown to play a role in regulating bone homeostasis. However, the contribution of EphB/ephrin-B molecules in human MSC function remains to be determined. In the present study, EphB and ephrin-B molecules were expressed by ex vivo expanded human MSC populations and within human bone marrow trephine samples. To elucidate the contribution of EphB/ephrin-B molecules in MSC recruitment, we performed functional spreading and migration assays and showed that reverse ephrin-B signalling inhibited MSC attachment and spreading by activating Src-, PI3Kinase- and JNK-dependent signalling pathways. In contrast, forward EphB2 signalling promoted MSC migration by activating the Src kinase- and Abl-dependent signalling pathways. Furthermore, activation of ephrin-B1 and/or ephrin-B2 molecules expressed by MSC was found to increase osteogenic differentiation, while ephrin-B1 activation promoted chondrogenic differentiation. These observations suggest that EphB/ephrin-B interactions may mediate the recruitment, migration and differentiation of MSC during bone repair. (C) 2010 Elsevier Inc. All rights reserved.