Endothelin-1 differentially directs lineage specification of adipose- and bone marrow-derived mesenchymal stem cells

Blood vessels composed of endothelial cells (ECs) contact with mesenchymal stem cells (MSCs) in different tissues, suggesting possible interaction between these 2 types of cells. We hypothesized that endothelin-1 (ET1), a secreted paracrine factor of ECs, can differentially direct the lineages of adipose-derived stem cells (ASCs) and bone marrow-derived MSCs (BMSCs). Predifferentiated ASCs and BMSCs were treated with ET1 for 2 cell passages and then induced for multilineage differentiation. Our results showed that adipogenesis of ET1-pretreated ASCs and osteogenesis of ET1-pretreated BMSCs were increased compared to those of control cells. The effect of ET1 on enhancing adipogenesis of ASCs and osteogenesis of BMSCs was attenuated by blocking endothelin receptor type A (ETAR) and/or endothelin receptor type B (ETBR). Western blot analysis indicated that regulation by ET1 was mediated through activation of the protein kinase B and ERK1/2 signaling pathways. We analyzed subpopulations of ASCs and BMSCs with or without ETAR and/or ETBR, and we found that ETAR(+)/ETBR- and ETAR(-)/ETBR+ subpopulations of ASCs and those of BMSCs pretreated with ET1 were prone to turning into adipocytes and osteoblasts, respectively, after differentiation induction. Our findings provide insight into the differential regulation of MSC specification by ET1, which may help develop viable approaches for tissue regeneration.Lee, M.-S., Wang, J., Yuan, H., Jiao, H., Tsai, T.-L., Squire, M. W., Li, W.-J. Endothelin-1 differentially directs lineage specification of adipose- and bone marrow-derived mesenchymal stem cells.