Notch Signaling Augments BMP9-Induced Bone Formation by Promoting the Osteogenesis-Angiogenesis Coupling Process in Mesenchymal Stem Cells (MSCs)

被引：82

作者：

Liao, Junyi ^{[1
,2
,3
,4
,5
]}

Wei, Qiang ^{[5
,6
,7
]}

Zou, Yulong ^{[5
,6
,7
]}

Fan, Jiaming ^{[5
,6
,7
]}

Song, Dongzhe ^{[5
,8
]}

Cui, Jing ^{[5
,6
,7
]}

Zhang, Wenwen ^{[5
,9
]}

Zhu, Yunxiao ^{[10
]}

Ma, Chao ^{[5
,11
,12
]}

Hu, Xue ^{[1
,2
,3
,4
,5
]}

Qu, Xiangyang ^{[5
,6
,7
]}

Chen, Liqun ^{[1
,2
,3
,4
,5
]}

Yu, Xinyi ^{[1
,2
,3
,4
,5
]}

Zhang, Zhicai ^{[5
,10
]}

Wang, Claire ^{[5
]}

Zhao, Chen ^{[1
,2
,3
,4
,5
]}

Zeng, Zongyue ^{[5
,6
,7
]}

Zhang, Ruyi ^{[5
,6
,7
]}

Yan, Shujuan ^{[5
,6
,7
]}

Wu, Tingting ^{[5
,11
,12
]}

Wu, Xingye ^{[1
,2
,3
,4
,5
]}

Shu, Yi ^{[5
,6
,7
]}

Lei, Jiayan ^{[1
,2
,3
,4
,5
]}

Li, Yasha ^{[5
,6
,7
]}

Luu, Hue H. ^{[5
]}

Lee, Michael J. ^{[5
]}

Reid, Rusell R. ^{[5
,13
]}

Ameer, Guillermo A. ^{[10
,14
]}

Wolf, Jennifer Moriatis ^{[5
]}

He, Tong-Chuan ^{[5
,6
,7
]}

Huang, Wei ^{[1
,2
,3
,4
]}

机构：

[1] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthopaed Surg, Chongqing 400016, Peoples R China

[2] Chongqing Med Univ, Affiliated Hosp 1, Dept Blood Transfus, Chongqing, Peoples R China

[3] Chongqing Med Univ, Affiliated Hosp 1, Dept Nephrol, Chongqing, Peoples R China

[4] Chongqing Med Univ, Affiliated Hosp 1, Dept Gen Surg, Chongqing, Peoples R China

[5] Univ Chicago, Med Ctr, Dept Orthopaed Surg & Rehabil Med, Mol Oncol Lab, Chicago, IL 60637 USA

[6] Chongqing Med Univ, Minist Educ, Key Lab Diagnost Med, Chongqing, Peoples R China

[7] Chongqing Med Univ, Affiliated Hosp, Chongqing, Peoples R China

[8] Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, State Key Lab Oral Dis, Chengdu, Peoples R China

[9] Binzhou Med Univ, Affiliated Yantai Hosp, Dept Lab Med & Clin Diagnost, Yantai, Peoples R China

[10] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA

[11] Wuhan Univ, Affiliated Zhongnan Hosp, Dept Neurosurg, Wuhan, Peoples R China

[12] Wuhan Univ, Affiliated Zhongnan Hosp, Dept Otolaryngol Head & Neck Surg, Wuhan, Peoples R China

[13] Univ Chicago, Med Ctr, Dept Surg, Sect Plast Surg, Chicago, IL 60637 USA

[14] Feinberg Sch Med, Dept Surg, Chicago, IL USA

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2017年 / 41卷 / 05期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

BMP9; signaling; Notch signaling; Osteogenesis; angiogenesis coupling; Mesenchymal stem cells; Bone repair; Regenerative medicine; HUMAN OSTEOSARCOMA GROWTH; MORPHOGENETIC PROTEINS; OSTEO/ODONTOBLASTIC DIFFERENTIATION; OSTEOBLAST DIFFERENTIATION; ADIPOSE-TISSUE; TUMOR-GROWTH; BMP9; PROLIFERATION; PATHWAY; WNT;

D O I：

10.1159/000471945

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background/Aims: Mesenchymal stem cells (MSCs) are multipotent progenitors that activation of BMP9 and Notch signaling yields effective osteogenesis-angiogenesis coupling in MSCs. Methods: Recently-characterized immortalized mouse adipose-derived progenitors (iMADs) were used as MSC source. Transgenes BMP9, NICD and dnNotch1 were expressed Osteogenic activity was assessed by in vitro assays and in vivo ectopic bone formation model.Results: BMP9 upregulated expression of Notch receptors and ligands in iMADs. Constitutively-active form of Notch1 NICD1 enhanced BMP9-induced osteogenic differentiation both in vitro and in vivo, which was effectively inhibited by dominant-negative form of Notch1 dnNotch1. BMP9-and NICD1-transduced MSCs implanted with a biocompatible scaffold yielded highly mature bone with extensive vascularization. NICD1 enhanced BMP9-induced expression of key angiogenic regulators in iMADs and Vegfa in ectopic bone, which was blunted by dnNotch1. Conclusion: Notch signaling may play an important role in BMP9-induced osteogenesis and angiogenesis. It's conceivable that simultaneous activation of the BMP9 and Notch pathways engineering. (C) 2017 The Author( s) Published by S. Karger AG, Basel.

引用

页码：1905 / 1923

页数：19

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