Open AccessCross‐talk between EGF and BMP 9 signalling pathways regulates the osteogenic differentiation of mesenchymal stem cells
Author(s) -
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 TongChuan,
Li Ming
Publication year - 2013
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12097
Subject(s) - microbiology and biotechnology , mesenchymal stem cell , progenitor cell , epidermal growth factor , biology , signal transduction , cellular differentiation , bmpr2 , bone morphogenetic protein , stem cell , chemistry , receptor , biochemistry , gene
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.