EphB4 Promotes Osteogenesis of CTLA4-Modified Bone Marrow-Derived Mesenchymal Stem Cells Through Cross Talk with Wnt Pathway in Xenotransplantation
EphB4 Promotes Osteogenesis of CTLA4-Modified Bone Marrow-Derived Mesenchymal Stem Cells Through Cross Talk with Wnt Pathway in Xenotransplantation
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EphB4 在异种移植中通过与 Wnt 通路相互作用促进 CTLA4 修饰的骨髓间充质干细胞的成骨
DOI：
10.1089/ten.tea.2015.0012
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Dai, Fei
中科院分区：
文献类型：
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作者：
Sun, Dong;Dong, Shiwu;Xu, Jianzhong;Dai, Fei
背景资料：细胞毒性T淋巴细胞相关抗原4-IG（CTLA 4-IG）修饰的骨髓间充质干细胞（MSCs-CTLA 4）在异种移植中具有良好的成骨功能，但其作用机制尚不清楚。由于促红细胞生成素肝细胞受体B4（EphB 4）和ephrinB 2之间的双向信号传导对于骨重建至关重要，本研究旨在充分表征MSCs-CTLA 4通过EphB 4/ephrinB 2及其与Wnt/β-catenin通路的相互作用在异种移植中促进骨再生的作用。方法：采用异种移植的方法，观察MSCs-CTLA 4的成骨能力。在成骨诱导条件下，用ephrinB 2-FC或FC处理MSCs-CTLA 4，并在有或无植物血凝素和外周血单个核细胞建立的免疫活化条件下进行体外培养。成骨标志物和Wnt通路相关分子如EphB 4、runt相关转录因子2（Runx.
Background: Cytotoxic T lymphocyte-associated antigen 4-Ig (CTLA4-Ig)-modified bone marrow-derived mesenchymal stem cells (MSCs-CTLA4) have excellent osteogenic function in xenografts, but their mechanism of action remains to be elucidated. As bidirectional signaling between erythropoietin-producing hepatocyte receptors B4 (EphB4) and ephrinB2 is vital for bone remodeling, this study aimed to fully characterize the role of MSCs-CTLA4 in promoting bone regeneration in xenotransplantation through EphB4/ephrinB2 and their cross talk with the Wnt/beta-catenin pathway. Methods: MSCs-CTLA4 were investigated for their osteogenic capacity through xenotransplantation in vivo. MSCs-CTLA4 were treated with ephrinB2-FC or FC under conditions of osteogenic induction and cultured with or without immune activation conditions established by phytohemagglutinin and peripheral blood mononuclear cells in vitro. Osteogenesis markers and the Wnt pathway-related molecules such as EphB4, runt-related transcription factor 2 (Runx...