文献类型：期刊文献

英文题名：The effect of gap junction-mediated transfer of miR-200b on osteogenesis and angiogenesis in a co-culture of MSCs and HUVECs

作者：Fan, Xiaoting[1];Teng, Yi[1];Ye, Zhaoyang[1];Zhou, Yan[1];Tan, Wen-Song[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2018

卷号：131

期号：13

外文期刊名：JOURNAL OF CELL SCIENCE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000443422700011)】；

基金：This research was supported by the National Natural Science Foundation of China (grant no. 31170951 and 81671841), the Natural Science Foundation of Shanghai (grant no. 16ZR1408700) and the Key Project of Science and Technology of Shanghai (grant no. 16JC1400203).

语种：英文

外文关键词：Pre-vascularized bone; Mesenchymal stem cell; Endothelial cell; Gap junction; miR-200b

摘要：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 can serve as intercellular signals that allow cell-cell communication. Here, the role of the transfer of the microRNA miR-200b between vasculogenic and osteogenic cells was explored in a co-culture system. Rat bone-marrow derived mesenchymal stem cells (BMSCs) formed functional gap junctions composed of connexin 43 (Cx43, also known as GJA1) with human umbilical vein endothelial cells (HUVECs), through which miR-200b could 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 increased osteogenic differentiation. Once inside HUVECs, miR-200b reduced the angiogenic potential of HUVECs through downregulation of ZEB2, ETS1, KDR and GATA2. Additionally, TGF-beta was found to trigger the transfer of miR-200b to HUVECs. Upon adding the TGF-beta inhibitor SB431542 or TGF-beta-neutralizing antibody, the formation of capillary-like structures in co-culture could be partially rescued. These findings may be fundamental to the development of a cell-based bone regeneration strategy.