Document Type
Journal Article
Department/Unit
School of Chinese Medicine
Title
EGFL7 is expressed in bone microenvironment and promotes angiogenesis via ERK, STAT3, and integrin signaling cascades
Language
English
Abstract
© 2014 Wiley Periodicals, Inc.Angiogenesis plays a pivotal role in bone formation, remodeling, and fracture healing. The regulation of angiogenesis in the bone microenvironment is highly complex and orchestrated by intercellular communication between bone cells and endothelial cells. Here, we report that EGF-like domain 7 (EGFL7), a member of the epidermal growth factor (EGF) repeat protein superfamily is expressed in both the osteoclast and osteoblast lineages, and promotes endothelial cell activities. Addition of exogenous recombinant EGFL7 potentiates SVEC (simian virus 40-transformed mouse microvascular endothelial cell line) cell migration and tube-like structure formation in vitro. Moreover, recombinant EGFL7 promotes angiogenesis featuring web-like structures in ex vivo fetal mouse metatarsal angiogenesis assay. We show that recombinant EGFL7 induces phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), signal transducer and activator of transcription 3 (STAT3), and focal adhesion kinase (FAK) in SVEC cells. Inhibition of ERK1/2 and STAT3 signaling impairs EGFL7-induced endothelial cell migration, and angiogenesis in fetal mouse metatarsal explants. Bioinformatic analyses indicate that EGFL7 contains a conserved RGD/QGD motif and EGFL7-induced endothelial cell migration is significantly reduced in the presence of RGD peptides. Moreover, EGFL7 gene expression is significantly upregulated during growth plate injury repair. Together, these results demonstrate that EGFL7 expressed by bone cells regulates endothelial cell activities through integrin-mediated signaling. This study highlights the important role that EGFL7, like EGFL6, expressed in bone microenvironment plays in the regulation of angiogenesis in bone.
Publication Date
2015
Source Publication Title
Journal of Cellular Physiology
Volume
230
Issue
1
Start Page
82
End Page
94
Publisher
Wiley
DOI
10.1002/jcp.24684
Link to Publisher's Edition
ISSN (print)
00219541
ISSN (electronic)
10974652
Recommended Citation
Chim, Shek Man, Vincent Kuek, Siu To Chow, Bay Sie Lim, Jennifer Tickner, Jinmin Zhao, Rosa Chung, Yu-Wen Su, Ge Zhang, Wendy Erber, Cory J. Xian, Vicki Rosen, and Jiake Xu. "EGFL7 is expressed in bone microenvironment and promotes angiogenesis via ERK, STAT3, and integrin signaling cascades." Journal of Cellular Physiology 230.1 (2015): 82-94.