AbstractsBiology & Animal Science

Effects of Na/K-ATPase and Its Ligands on Bone Marrow Mesenchymal Stem Cell Differentiation

by Moustafa Sayed




Institution: University of Toledo Health Science Campus
Department: College of Medicine
Degree: PhD
Year: 2014
Keywords: Biomedical Research
Record ID: 2030859
Full text PDF: http://rave.ohiolink.edu/etdc/view?acc_num=mco1396351646


Abstract

Reported increases of endogenous ligands for Na/K-ATPase induced during kidney dysfunction and heart failure, as well as the role of Na/K-ATPase signaling function in stem cell differentiation, lead us to conduct this study in order to evaluate whether Na/K-ATPase activation through its ligands and associated signaling functions affect bone marrow mesenchymal stem cells (BMSCs) differentiation capacity. BMSCs were isolated from male Sprague-Dawley rats and cultured as described in the materials and methods chapter. The results revealed that marinobufagenin (MBG), a specific Na/K-ATPase ligand, potentiated rosiglitazone-induced adipogenesis in BMSCs. Meanwhile, it attenuated BMSCs osteogenesis. Mechanistically, we found that MBG increases the protein expression of CCAAT/enhancer binding protein alpha (C/EBPa) through the activation of an extracellular regulated kinase (ERK) signaling pathway, which in turn leads to enhanced rosiglitazone-induced adipogenesis. The effect of MBG on C/EBPa expression and on rosiglitazone-induced adipogenesis was blocked by the inhibition of the activation of ERK through use of the inhibitor U0126. Reciprocally, MBG reduced runt-related transcription factor 2 (RunX2) expression which resulted in the inhibition of ß-glycerophosphate/ascorbic acid induced osteogenesis. Moreover, MBG potentiated rosiglitazone-induced adipogenesis in 3T3-L1 cells and in mouse BMSCs. In addition, we found that MBG increased the expression of type-1 collagen in rat BMSCs. These results suggest that Na/K-ATPase and its signaling functions are involved in the regulation of BMSCs differentiation.