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Cited by 2,742

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

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

Open access
Liao, Junyi, Wei, Qiang, Zou, Yulong, Fan, Jiaming, Song, Dongzhe, Cui, Jing, Zhang, Wenwen, Zhu, Yunxiao, Ma, Chao, Hu, Xue, Qu, Xiangyang, Chen, Liqun, Yu, Xinyi, Zhang, Zhicai, Wang, Claire, Zhao, Chen, Zeng, Zongyue, Zhang, Ruyi, Yan, Shujuan, Wu, Tingting, Wu, Xingye, Shu, Yi, Lei, Jiayan, Li, Yasha, Luu, Hue H., Lee, Michael J., Reid, Russell R., Ameer, Guillermo A., Wolf, Jennifer Moriatis, He, Tong-Chuan, Huang, Wei·2017·Cellular Physiology and Biochemistry
DOI 10.1159/000471945
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Abstract

Background/Aims: Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate into several lineages including bone. Successful bone formation requires osteogenesis and angiogenesis coupling of MSCs. Here, we investigate if simultaneous 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 by adenoviral vectors. Gene expression was determined by qPCR and immunohistochem¡stry. 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 should efficiently couple osteogenesis and angiogenesis of MSCs for successful bone tissue engineering.

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Metadata

Authors
Liao, J., Wei, Q., Zou, Y., Fan, J., Song, D., Cui, J., Zhang, W., Zhu, Y., Ma, C., Hu, X., Qu, X., Chen, L., Yu, X., Zhang, Z., Wang, C., Zhao, C., Zeng, Z., Zhang, R., Yan, S., Wu, T., Wu, X., Shu, Y., Lei, J., Li, Y., Luu, H. H., Lee, M. J., Reid, R. R., Ameer, G. A., Wolf, J. M., He, T.-C., & Huang, W.
Venue
Cellular Physiology and Biochemistry
Publisher
S. Karger AG
Published
2017
Volume
41
Issue
5
Pages
1905-1923
ISSN
  • 1015-8987 (ISSN-L)
  • 1421-9778
DOI
10.1159/000471945
OpenAlex
W2605187236
Cited by
2,742
References
2
FWCI
126.33
Type
journal article
Language
en
Open access
gold

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