Open AccessGap junction-mediated MiR-200b on osteogenesis and angiogenesis in coculture between MSCs and HUVECs
Author(s) -
Xiaoran Fan,
Yi Teng,
Zhaoyang Ye,
Yan Zhou,
WenSong Tan
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.216135
Subject(s) - microbiology and biotechnology , angiogenesis , biology , mesenchymal stem cell , umbilical vein , connexin , downregulation and upregulation , immunology , gap junction , in vitro , cancer research , intracellular , biochemistry , gene
For successful engineering of pre-vascularized bone tissue in vitro, understanding the interactions between vasculogenic cells and bone-forming cells is a prerequisite. Mounting evidence indicates that microRNAs serve as the intercellular signals that allow cell-cell communication. Here, a new transfer machine, miR-200b, was explored in a coculture system between vasculogenic and osteogenic cells. Rat bone-marrow derived mesenchymal stem cells (BMSCs) formed functional gap junctions composed of connexin 43 (Cx43) with human umbilical vein endothelial cells (HUVECs), through which miR-200b can transfer from BMSCs to HUVECs to regulate osteogenesis and angiogenesis. As a negative regulator, the decrease in miR-200b level in BMSCs derepressed the expression of VEGF-A, leading to promoted osteogenic differentiation. Once inside HUVECs, miR-200b blunted the angiogenic potential of HUVECs by down-regulation of ZEB 2, ETS 1, KDR and GATA 2. Additionally, TGF-β was found to trigger the transfer of miR-200b to HUVECs. By adding TGF-β inhibitor SB431542 or neutralizing antibody, the formation of capillary-like structure in coculture could be partially rescued. These findings may be fundamental to the development of cell-based bone regeneration strategy.