Periostin: A Downstream Mediator of EphB4-Induced Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells.
Periostin: A Downstream Mediator of EphB4-Induced Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells.
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Periostin：EphB4 诱导人骨髓间充质干细胞成骨分化的下游介质。
DOI：
10.1155/2016/7241829
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发表时间：
2016
影响因子：
4.3
通讯作者：
Dai F
中科院分区：
文献类型：
--
作者：
Zhang F;Zhang Z;Sun D;Dong S;Xu J;Dai F
促红细胞生成素肝细胞B4（EphB 4）已被报道是调节骨稳态的关键分子开关，但其潜在机制仍知之甚少。在这项研究中，我们研究了EphB 4在骨髓间充质干细胞（MSCs）中调控骨膜蛋白（POSTIN）表达的作用，并评估其体外成骨诱导的作用和分子机制。ephrinB 2-FC处理可显著增加MSCs中POR 4的表达，而抑制EphB 4则可消除这种作用。此外，成骨标志物上调，特别是在过表达EphB 4的MSC中。为了阐明EphB 4和Wnt通路之间的串扰的潜在机制，我们检测了磷酸化糖原合成酶激酶3β-丝氨酸9（p-GSK-3β-Ser 9）和β-连环蛋白以及成骨标志物Runx 2和COL 1的蛋白表达的变化。结果显示，ephrinB 2-FC可下调MSCs中GSK-3β的活化和成骨标志物的表达水平，而阻断整合素αvβ3可抑制这种作用。我们的研究结果表明，EphB 4可以促进骨髓间充质干细胞的成骨分化，通过上调POR 4的表达。这不仅有助于揭示EphB 4与Wnt信号通路的相互作用机制，而且有助于更好地理解EphB 4/ephrinB 2信号通路在骨稳态中的作用。
Erythropoietin-producing hepatocyte B4 (EphB4) has been reported to be a key molecular switch in the regulation of bone homeostasis, but the underlying mechanism remains poorly understood. In this study, we investigated the role of EphB4 in regulating the expression of periostin (POSTN) within bone marrow-derived mesenchymal stem cells (MSCs) and assessed its effect and molecular mechanism of osteogenic induction in vitro. Treatment with ephrinB2-FC significantly increased the expression of POSTN in MSCs, and the inhibition of EphB4 could abrogate this effect. In addition, osteogenic markers were upregulated especially in MSCs overexpressing EphB4. To elucidate the underlying mechanism of cross talk between EphB4 and the Wnt pathway, we detected the change in protein expression of phosphorylated-glycogen synthase kinase 3β-serine 9 (p-GSK-3β-Ser9) and β-catenin, as well as the osteogenic markers Runx2 and COL1. The results showed that GSK-3β activation and osteogenic marker expression levels were downregulated by ephrinB2-FC treatment, but these effects were inhibited by blocking integrin αvβ3 in MSCs. Our findings demonstrate that EphB4 can promote osteogenic differentiation of MSCs via upregulation of POSTN expression. It not only helps to reveal the interaction mechanism between EphB4 and Wnt pathway but also brings a better understanding of EphB4/ephrinB2 signaling in bone homeostasis.