Modulation of MAPK signalling by immobilized adhesive peptides: Effect on stem cell response to XXXX -derived peptides.

@entity2447 @entity19 @entity8386 @entity4351 @entity14032 @entity15864 @entity1995 @entity39040 @entity8837
UNASSIGNED: Biomimetic materials were developed to regulate stem cell behaviour. We have analyzed the influence of @entity4351 ( @entity4351 ) films, functionalized with adhesive peptides derived from fibronectin (pFibro) or bone sialoprotein (pBSP), on the response of @entity19 multipotent C3H10T1/2 cells to @entity15864 ( @entity15864 ) and its derived peptides (pBMP-9 and SpBMP-9). @entity4351 -pFibro promoted better cell cytoskeleton organization and faster focal adhesion kinase activation than did @entity4351 -pBSP. @entity4351 -pFibro also promoted MAPK signalling to improve the cell response to @entity15864 by inactivating @entity8837 and stimulating @entity1995 and @entity14032 . @entity15864 , pBMP-9 and SpBMP-9 induced greater phosphorylation of @entity8386 /8 in cells attached to @entity4351 -pFibro than in cells on @entity4351 -pBSP. These phosphorylated @entity39040 were translocated to the nucleus. @entity15864 and its derived peptides restored the phosphorylation of @entity14032 in cells on @entity4351 -pBSP, but it remained less phosphorylated than in cells on @entity4351 -pFibro stimulated with pBMP-9 and SpBMP-9. Cells attached to @entity4351 -pFibro contained more @entity2447 , essential for stem cell commitment to become osteoblasts, than did cells on @entity4351 -pBSP when incubated with @entity15864 and its derived peptides. @entity2447 was no longer detected when the cells were pre-treated with @entity14032 inhibitor. Therefore pFibro plus @entity15864 and its derived peptides may be a promising strategy to develop biomimetic materials. STATEMENT OF SIGNIFICANCE: Biomaterials functionalized with adhesive peptides to favour bone repair have generated a great interest over the past decade. However, the effect of these materials on the ability of cells to respond to growth factors remains poorly known. One major growth factor subfamily involved in bone formation is the bone morphogenetic protein (BMP). However, these BMPs are expensive. We therefore developed less costly derived molecules. We showed how adhesive peptides derived from bone matrix proteins grafted onto polymer films affect the intracellular signalling and thus the ability of stem cells to be activated by BMP and its derived molecules. We have therefore identified a combination of bioactive polymers and BMP molecules that direct the stem cells towards bone forming cells.
