Cross‐talk between EGF and BMP 9 signalling pathways regulates the osteogenic differentiation of mesenchymal stem cells

Abstract Mesenchymal stem cells ( MSC s) are multipotent progenitors, which give rise to several lineages, including bone, cartilage and fat. Epidermal growth factor ( EGF ) stimulates cell growth, proliferation and differentiation. EGF acts by binding with high affinity to epidermal growth factor r...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cellular and molecular medicine 2013-09, Vol.17 (9), p.1160-1172
Main Authors: Liu, Xing, Qin, Jiaqiang, Luo, Qing, Bi, Yang, Zhu, Gaohui, Jiang, Wei, Kim, Stephanie H., Li, Mi, Su, Yuxi, Nan, Guoxin, Cui, Jing, Zhang, Wenwen, Li, Ruidong, Chen, Xiang, Kong, Yuhan, Zhang, Jiye, Wang, Jinhua, Rogers, Mary Rose, Zhang, Hongyu, Shui, Wei, Zhao, Chen, Wang, Ning, Liang, Xi, Wu, Ningning, He, Yunfeng, Luu, Hue H., Haydon, Rex C., Shi, Lewis L., Li, Tingyu, He, Tong‐Chuan, Li, Ming
Format: Article
Language:English
Subjects:
Adenoviruses
Bone growth
Bone morphogenetic protein 9
Cartilage
Cell differentiation
Cell growth
Cell proliferation
Cell surface
Drug dosages
Epidermal growth factor
Epidermal growth factor receptors
Explants
Gefitinib
Implantation
Inhibitors
Investigations
Kinases
Mesenchymal stem cells
Mesenchyme
Metastasis
Ossification (ectopic)
Osteogenesis
Phosphatase
Protein-tyrosine kinase receptors
Proteins
Regenerative medicine
Signal transduction
Stem cell transplantation
Stem cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Mesenchymal stem cells ( MSC s) are multipotent progenitors, which give rise to several lineages, including bone, cartilage and fat. Epidermal growth factor ( EGF ) stimulates cell growth, proliferation and differentiation. EGF acts by binding with high affinity to epidermal growth factor receptor ( EGFR ) on the cell surface and stimulating the intrinsic protein tyrosine kinase activity of its receptor, which initiates a signal transduction cascade causing a variety of biochemical changes within the cell and regulating cell proliferation and differentiation. We have identified BMP 9 as one of the most osteogenic BMP s in MSC s. In this study, we investigate if EGF signalling cross‐talks with BMP 9 and regulates BMP 9‐induced osteogenic differentiation. We find that EGF potentiates BMP 9‐induced early and late osteogenic markers of MSC s in vitro , which can be effectively blunted by EGFR inhibitors Gefitinib and Erlotinib or receptor tyrosine kinase inhibitors AG ‐1478 and AG ‐494 in a dose‐ and time‐dependent manner. Furthermore, EGF significantly augments BMP 9‐induced bone formation in the cultured mouse foetal limb explants. In vivo stem cell implantation experiment reveals that exogenous expression of EGF in MSC s can effectively potentiate BMP 9‐induced ectopic bone formation, yielding larger and more mature bone masses. Interestingly, we find that, while EGF can induce BMP 9 expression in MSC s, EGFR expression is directly up‐regulated by BMP 9 through Smad1/5/8 signalling pathway. Thus, the cross‐talk between EGF and BMP 9 signalling pathways in MSC s may underline their important roles in regulating osteogenic differentiation. Harnessing the synergy between BMP 9 and EGF should be beneficial for enhancing osteogenesis in regenerative medicine.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.12097