Sanz C, Vázquez P, Blázquez C, Barrio PA, Alvarez MM, Blázquez 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␥, C/EBP␤, AP2, and LPL in a time-dependent pattern. Notably, GLP-1 significantly reduced the expression of PPAR␥, C/EBP␤, 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.human mesenchymal stem cell; proliferation; adipogenesis; cytoprotection MESENCHYMAL STEM CELLS (MSCs) from bone marrow were initially described as clonal (30) cells capable of differentiating into adipocytes, chondrocytes, osteoblasts (30), and insulinsecreting cells (39). Although the ability of stem cells to proliferate and differentiate into several cell lines is well known, the mechanisms and the molecules involved in such processes are poorly understood. The candidates for such activity are likely to be a number of structurally related peptide hormones and neuropeptides that exert cytoprotective and proliferative effects through G protein-coupled receptor activation. Furthermore, several peptides related to the glucagonsecretin family, together with other peptides, exert either pro-or antiapoptotic actions on several cell types (10).Glucagon-like peptide 1 (GLP-1) is encoded by the proglucagon gene, which is secreted by gut L cells and some brain neurons. It exerts multiple biological effects on peripheral tissues and the central nervous system (2, 3, 25, 18). Thus, G...

The gas-liquid transition of a "quenched-annealed"(QA) system is studied by grand-canonical Monte Carlo simulation. The "quenched" particles are hard spheres within configurations chosen randomly from those of an equilibrium hard-sphere system at given density. The fluid particles interact with the matrix particles by a hard-core potential and with each other by a hard-core potential and an additional potential of a Lennard-Jones type. Our results are in good qualitative agreement with various theoretical approaches. With increasing matrix density the critical temperature is lowered compared to that of the bulk system and the gap between the gas and liquid densities narrowed. Our simulations confirm, for this QA system, the possibility of two fluid-fluid transitions substituting for the unique gas-liquid transition of the bulk system. They demonstrate the necessity to average over a significant number of matrix realizations in order to obtain a quantitative location of the phase coexistence lines.

We report on the synthesis and properties of a photoactivatable caged RGD peptide and its application for phototriggering integrin and cell binding to surfaces. We analyzed in detail (i) the differences in the integrin binding affinity of the caged and uncaged forms via quartz crystal microbalance (QCM) studies, (ii) the efficiency and yield of the photolytic uncaging reaction, (iii) the biocompatibility of the photolysis byproducts and irradiation conditions and (iv) the possibility of site, temporal and density control of integrin binding and, therefore, human cell attachment, (v) the possibility of in situ generation of cell patterns and cell gradients by controlling the exposure. These studies provide a clear picture of the potential and limitations of caged ligands for integrin-mediated cell adhesion and demonstrate the application of this approach to control and study other types of cell interactions and response.

Phase separation in mixtures of a rodlike colloid and two or more rodlike polymersWe have tested the capabilities of a new self-consistent integral equation, closely connected with Verlet's modified closure, for the study of fluid-fluid phase separation in symmetric non-additive hard-sphere mixtures. New expressions to evaluate the chemical potential of mixtures are presented and play a key role in the construction of the phase diagram. The new integral equation, which implements consistency between virial and fluctuation theorem routes to the isothermal compressibility, together with chemical potential and virial pressure consistency via the Gibbs-Duhem relation, yields a phase diagram which especially at high densities agrees remarkably well with the new semi-Grand Ensemble Monte Carlo simulation data also presented in this work. Deviations close to the critical point can be understood as a consequence of the inability to enforce virial-fluctuation consistency in the neighborhood of the spinodal decomposition curve.