title: Effect of BMP-2 and/or BMP-9 on preosteoblasts attached to polycaprolactone functionalized by adhesive peptides derived from bone sialoprotein.
abstract: Biomaterials functionalized by adhesive peptides improve the cell-substratum interaction. However, their influence on the response of cells to growth factors is still poorly understood. We have shown that bone morphogenetic protein (BMP) 2 activates the Smad pathway only in murine MC3T3-E1 preosteoblasts attached to polycaprolactone (PCL) film functionalized by RGD peptides derived from bone sialoprotein (pRGD). We have now analysed the way recombinant human BMP-2 and/or BMP-9 (0.38 nM) influence the signal transduction and differentiation of MC3T3-E1 preosteoblasts attached to PCL-pRGD. While kinetics of MAPK activation were similar in cells treated by BMP-2 and BMP-9, different kinetics of Smad activation and β-catenin stabilization were observed. BMP-2 induced Smad1/5/8 phosphorylation within 0.5 and BMP-9 within 4 h, while the β-catenin was lower at 2 h only in cells treated with BMP-9. However, both BMPs induced the translocation of phosphorylated Smad1/5/8 to the nucleus at 4 h and increased Dlx5, osterix and osteocalcin transcripts as well as alkaline phosphatase activity at 72 h. A BMP-2/BMP-9 combination that maintained the β-catenin amount constant but reduced that of phosphorylated Smad within 4 h had quite similar effect than BMP-2 alone. It is therefore important to determine how biomimetic materials influence the response of cells to BMPs.
authors.affiliation: Cell-Biomaterial Biohybrid Systems, Department of Chemical Engineering and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, 2500 boul. de l'Université, Sherbrooke, Québec, Canada J1K 2R1.
authors.forename: Olivier
authors.initials: O
authors.lastname: Drevelle
authors.forename: Alex
authors.initials: A
authors.lastname: Daviau
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Lauzon
authors.forename: Nathalie
authors.initials: N
authors.lastname: Faucheux
mesh_terms: D000268:Adhesiveness; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D055427:Growth Differentiation Factor 2 / Q000494:pharmacology*; D058574:Integrin-Binding Sialoprotein / Q000737:chemistry*; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011091:Polyesters / Q000737:chemistry*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; C526108:Gdf2 protein, mouse; D055427:Growth Differentiation Factor 2; D058574:Integrin-Binding Sialoprotein; D009842:Oligopeptides; D011091:Polyesters; C016240:polycaprolactone; C047981:arginyl-glycyl-aspartic acid