Signaling and biological effects of glucagon-like peptide 1 on the differentiation of mesenchymal stem cells from human bone marrow

Sanz C, Vazquez P, Blazquez C, Barrio PA, Alvarez MM, Blazquez E. Signaling and biological effects of glucagon-like peptide 1 on the differentiation of mesenchymal stem cells from human bone marrow. Am J Physiol Endocrinol Metab 298: E634-E643, 2010. First published December 29, 2009; doi:10.1152/ajpendo.00460.2009.-Glucagon-like peptide 1 (GLP-1) functions as an incretin hormone with antidiabetogenic properties. However, the role of GLP-1 in human bone marrow-derived mesenchymal stem cells (hMSCs), if any, remains unknown. The effects of GLP-1 on hMSCs were tested with regard to cell proliferation, cytoprotection, and cell differentiation into adipocytes. The signaling pathways involved in these processes were also analyzed. Cells were characterized with biochemical and morphological approaches before and after being induced to differentiate into adipocytes. PCNA protein levels were used as a proliferation index, whereas cell apoptosis was studied by deprivation of fetal bovine serum. Isolated hMSCs expressed stem cell markers as well as mRNA and GLP-1 receptor protein. GLP-1 increased the proliferation of hMSCs, which decreased when they were induced to differentiate into adipocytes. This process produced biochemical and morphological changes in cells expressing PPAR gamma, C/EBP beta, AP2, and LPL in a time-dependent pattern. Notably, GLP-1 significantly reduced the expression of PPAR gamma, C/EBP beta, and LPL. These effects were exerted at least through the MEK and PKC signaling pathways. In addition, GLP-1 significantly reduced cell apoptosis. Our data indicate that, in hMSCs, GLP-1 promotes cellular proliferation and cytoprotection and prevents cell differentiation into adipocytes. These latter findings underscore the potential therapeutic role of GLP-1 in preventing the adipocyte hyperplasia associated with obesity and, additionally, could bolster the maintenance of hMSC stores by promoting the proliferation and cytoprotection of undifferentiated hMSC.