TY - JOUR A2 - Hart, David A. AU - Wu, Xiaohua AU - Ma, Mengjun AU - Wang, Peng AU - Xie, Zhongyu AU - Wang, Shan AU - Su, Hongjun AU - Deng, Wen AU - Feng, Pei AU - Su, Chunyan AU - Yang, Jiewen AU - Li, Jinteng AU - Tang, Su’an AU - Wu, Yanfeng AU - Shen, Huiyong PY - 2019 DA - 2019/02/07 TI - α2-HS Glycoprotein in Plasma Extracellular Vesicles Inhibits the Osteogenic Differentiation of Human Mesenchymal Stromal Cells In Vitro SP - 7246479 VL - 2019 AB - Extracellular vesicles (Evs) contain diverse functional proteins, mRNAs, miRNAs, and DNA fragments, are secreted by various types of cells, and play important roles in cellular communication. Here, we show for the first time that plasma Evs inhibited the osteogenic differentiation of mesenchymal stromal cells (MSCs) in vitro and the level of inhibition was positively correlated with the plasma Evs concentration. Plasma Evs downregulated the expression of markers such as osteocalcin (OCN), Runt-related transcription factor 2 (Runx2), and Osterix at mRNA levels required for osteogenic differentiation and reduced pSmad1/5/8 levels in MSCs. Furthermore, pSmad1/5/8 levels increased and MSCs underwent normal osteogenic differentiation after Evs-derived α2-HS glycoprotein (AHSG) function was inhibited with an anti-AHSG neutralizing antibody. However, the levels of pERK1/2, active β-catenin, and HES1 were not significantly altered. Therefore, we propose that as essential components of the extracellular microenvironment of MSCs, plasma Evs are taken up by MSCs and subsequently repress osteogenic differentiation through an AHSG-mediated decrease in pSmad1/5/8 levels. Our work identifies plasma Evs as novel regulators of MSC osteogenic differentiation. SN - 1687-966X UR - https://doi.org/10.1155/2019/7246479 DO - 10.1155/2019/7246479 JF - Stem Cells International PB - Hindawi KW - ER -