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Safrole oxide induced neuronal differentiation of rat bone-marrow mesenchymal stem cells by elevating Hsp70
Authors:YanChun Zhao  Jie Xin  ChunHui Sun  BaoXiang Zhao  Jing Zhao  Le Su
Institution:1. Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China;2. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan 250012, China;3. Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China
Abstract:In a previous study, we found that at low concentrations, safrole oxide (SFO) could induce vascular endothelial cell (VEC) transdifferentiation into neuron-like cells; however, whether SFO could induce bone-marrow mesenchymal stem cell (BMSC) neural differentiation was unknown. Here, we found that SFO could effectively induce BMSC neural differentiation in the presence of serum and fibroblast growth factor 2 and did not affect cell viability at low concentrations. The levels of neuron-specific enolase and neurofilament-L were increased greatly, but that of glial fibrillary acidic protein was absent with SFO treatment for 48 h. Furthermore, SFO could increase the level of heat shock protein 70 (Hsp70), an important factor in neuronal differentiation. Knockdown of Hsp70 by its small interfering RNA blocked SFO-induced BMSC differentiation. Thus, SFO is a novel inducer of BMSC differentiation to neuron-like cells and Hsp70 is implicated in the differentiation process. We provide a new tool for obtaining neuron-like cells from BMSCs and for further investigating the new effect of Hsp70 on BMSC neuronal differentiation.
Keywords:BMSC  bone-marrow mesenchymal stem cell  DMEM-LG  Dulbecco's modified Eagle's medium-low glucose  FBS  fetal bovine serum  FGF-2  fibroblast growth factor 2  GFAP  glial fibrillary acidic protein  Hsp70  heat shock protein 70  HUVEC  human umbilical vascular endothelial cell  MAP-2  microtubule associated proteins-2  NeuN  neuron-specific nuclear protein  NF-L  neurofilament-L  NSE  neuron-specific enolase  PBS  phosphate buffered saline  qPCR  quantitative real-time PCR  SFO  safrole oxide  Tuj-1  Neuron-specific class III beta-tubulin  VEC  vascular endothelial cell
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