Bidirectional juxtacrine ephrinB2/Ephs signaling promotes angiogenesis of ECs and maintains self-renewal of MSCs

被引：21

作者：

Cao, Cen ^{[1
]}

Huang, Ying ^{[2
]}

Tang, Qingming ^{[1
]}

Zhang, Chenguang ^{[1
]}

Shi, Lei ^{[2
]}

Zhao, Jiajia ^{[1
]}

Hu, Li ^{[1
]}

Hu, Zhewen ^{[2
]}

Liu, Yun ^{[2
]}

Chen, Lili ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Stomatol, Wuhan 430022, Hubei, Peoples R China

[2] Peking Univ, Sch & Hosp Stomatol, Dept Geriatr Dent, Beijing 100081, Peoples R China

来源：

BIOMATERIALS | 2018年 / 172卷

基金：

美国国家科学基金会; 国家重点研发计划;

关键词：

EphrinB2/Ephs; Angiogenesis; Self-renewal; Co-transplantation; Bone tissue engineering; MESENCHYMAL STEM-CELLS; MARROW STROMAL CELLS; ENDOTHELIAL-CELLS; TUMOR-GROWTH; BONE REPAIR; OSTEOBLASTS; PATHWAY; OSTEOGENESIS; RECRUITMENT; ANTAGONIZES;

D O I：

10.1016/j.biomaterials.2018.04.042

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Co-transplantation of endothelial cells (ECs) and mesenchymal stem cells (MSCs) is an important strategy for repairing complex and large bone defects. However, the ways in which ECs and MSCs interact remain to be fully clarified. We found that forward ephrinB2/Ephs signaling from hBMSCs to hUVECs promoted the tube formation of hUVECs by activating the PI3K/AKT/mTOR pathway. Reverse ephrinB2/Ephs signaling from hUVECs to hBMSCs promoted the proliferation and maintenance of hBMSCs self-renewal via upregulation of OCT4, SOX2, and YAP1. Subcutaneous co-transplantation of ECs and MSCs in nude mice confirmed that forward ephrinB2/Ephs signaling could increase the cross-sectional area of blood vessels in the transplanted area, and reverse ephrinB2/Ephs signaling could maintain the self-renewal of transplanted hBMSCs in vivo. Based on these results, ephrinB2/Ephs bidirectional juxtacrine regulation between ECs and MSCs plays a pivotal role in improving the healing of bone defects by promoting angiogenesis and achieving a sufficient number of MSCs. (C) 2018 Elsevier Ltd. All rights reserved.

引用

页码：1 / 13

页数：13

共 46 条

[31] The ephrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth [J].

Pennisi, Angela ;

Ling, Wen ;

Li, Xin ;

Khan, Sharmin ;

Shaughnessy, John D., Jr. ;

Barlogie, Bart ;

Yaccoby, Shmuel .

BLOOD, 2009, 114 (09) :1803-1812

[32] Marrow stromal cells as steam cells for nonhematopoietic tissues [J].

Prockop, DJ .

SCIENCE, 1997, 276 (5309) :71-74

[33] Essential Roles of EphB Receptors and EphrinB Ligands in Endothelial Cell Function and Angiogenesis [J].

Salvucci, Ombretta ;

Tosato, Giovanna .

GUIDANCE MOLECULES IN CANCER AND TUMOR ANGIOGENESIS, 2012, 114 :21-57

[34] EphrinB reverse signaling contributes to endothelial and mural cell assembly into vascular structures [J].

Salvucci, Ombretta ;

Maric, Dragan ;

Economopoulou, Matina ;

Sakakibara, Shuhei ;

Merlin, Simone ;

Follenzi, Antonia ;

Tosato, Giovanna .

BLOOD, 2009, 114 (08) :1707-1716

[35] Role of angiogenesis in bone repair [J].

Saran, Uttara ;

Piperni, Sara Gemini ;

Chatterjee, Suvro .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2014, 561 :109-117

[36] SOX2 Regulates YAP1 to Maintain Stemness and Determine Cell Fate in the Osteo-Adipo Lineage [J].

Seo, Eunjeong ;

Basu-Roy, Upal ;

Gunaratne, Preethi H. ;

Coarfa, Cristian ;

Lim, Dae-Sik ;

Basilico, Claudio ;

Mansukhani, Alka .

CELL REPORTS, 2013, 3 (06) :2075-2087

[37] Post-translational deregulation of YAP1 is genetically controlled in rat liver cancer and determines the fate and stem-like behavior of the human disease [J].

Simile, Maria M. ;

Latte, Gavinella ;

Demartis, Maria I. ;

Brozzetti, Stefania ;

Calvisi, Diego F. ;

Porcu, Alberto ;

Feo, Claudio F. ;

Seddaiu, Maria A. ;

Daino, Lucia ;

Berasain, Carmen ;

Tomasi, Maria L. ;

Avila, Matias A. ;

Feo, Francesco ;

Pascale, Rosa M. .

ONCOTARGET, 2016, 7 (31) :49194-49216

[38] P53 suppresses cell proliferation, metastasis, and angiogenesis of osteosarcoma through inhibition of the PI3K/AKT/mTOR pathway [J].

Song, Ruipeng ;

Tian, Ke ;

Wang, Weidong ;

Wang, Limin .

INTERNATIONAL JOURNAL OF SURGERY, 2015, 20 :80-87

[39] Bringing new life to damaged bone: The importance of angiogenesis in bone repair and regeneration [J].

Stegen, Steve ;

van Gastel, Nick ;

Carmeliet, Geert .

BONE, 2015, 70 :19-27

[40] Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses [J].

Stein, E ;

Lane, AA ;

Cerretti, DP ;

Schoecklmann, HO ;

Schroff, AD ;

Van Etten, RL ;

Daniel, TO .

GENES & DEVELOPMENT, 1998, 12 (05) :667-678

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