The emerging data show that the insulinotrophic hormone glucagon-like peptide-1(GLP-1) and its agonist extendin-4 have neurotrophic function to inducing neuronal differentiation of PC12 cells and prevent neurons damage challenged by oxidative stress. Here, with the model of high throughput screen for GLP-1 receptor agonists, we screen and identify that geniposide is a novel agonist for GLP-1 receptor. Furthermore, geniposide induces the neuronal differentiation of PC12 cells with resulting neurites outgrowth; we also observe an increase in expression of growth-associated protein-43. U0126, a selective MEK inhibitor, prevents neurites out growth and phosphorylation of mitogen-activated kinase proteins in PC12 cells induced by geniposide. All these results show that activation of GLP-1 receptor by geniposide to induce the neuronal differentiation of PC12 cells involves in MAPK signaling cascade.
Recent development of three-dimensional graphene foam (GF) with conductive and interconnected macroporous structure is attracting particular attention as platforms for tissue engineering. However, widespread application of GF as bone scaffolds is restricted due to its poor mechanical property and inert surface character. To overcome these drawbacks, in this study, a bilayered biopolymer coating was designed and successfully deposited covering the entire surface area of GF skeleton. A poly(lactic-co-glycolic acid) layer was first dip-coated to strengthen the GF substrate, followed by the electrophoretic codeposition of a hybrid layer, consisting of chitosan and BMP2, to functionalize GF with the ability to recruit and induce osteogenic differentiation of hMSC. Our data indicated that the mechanical property of GF was significantly increased without compromising the macroporous structure. Importantly, the immobilized BMP2 exhibited sustained and electroresponsive release profiles with rapid response to the electric field exerted on GF, which is beneficial to balancing BMP2 dose in a physiological environment. Moreover, the osteogenic differentiation of hMSC was significantly improved on the functionalized GF. Taking advantage of the unique macrostructure from GF as well as the superior mechanical properties and BMP2 release profile supported by the deposited coatings, it is therefore expected that the developed GF could be a promising alternative as innovative bone-forming favorable scaffolds.
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