title: Murine preosteoblast differentiation induced by a peptide derived from bone morphogenetic proteins-9.
abstract: Bone morphogenetic proteins (BMPs) increase the differentiation of osteoblasts implicated in bone formation and repair. In a previous study, we demonstrated that a peptide derived from BMP-9 (pBMP-9) at 400 ng/mL inhibited murine preosteoblasts MC3T3-E1 proliferation. Here, we compared the effects of equimolar concentrations of BMP-2 (50 ng/mL), BMP-9 (42.3 ng/mL), and pBMP-9 (4.52 ng/mL) on the differentiation of MC3T3-E1 in a serum-free medium. Like BMP-2, BMP-9 and pBMP-9 activated the Smad pathway. In contrary to BMP-2, the Smad phosphorylation induced by BMP-9 and pBMP-9 is not prevented by noggin, an extracellular antagonist of BMP-2. Further, BMP-9 and pBMP-9 increased, dose dependently, alkaline phosphatase activity, an early marker of osteoblast differentiation, after 1 day. Quantitative real-time polymerase chain reaction analysis demonstrated that BMP-2, BMP-9, and pBMP-9 (4.52 or 400 ng/mL) all activated the transcription of Runx2, Osterix, type I collagen alpha1 chain, and Osteocalcin genes within day 6. Alizarin red S quantification demonstrated that pBMP-9 (400 ng/mL) and pBMP-9 (4.52 ng/mL) allowed a slight deposition of Ca(2+) in the extracellular matrix of cells within 12 and 18 days, respectively. Therefore, pBMP-9 might be a promising replacement for costly BMP in tissue engineering applications that require a well-defined serum-free medium.
authors.affiliation: Laboratory of Cell-Biomaterial Biohybrid Systems, Department of Chemical Engineering and Biotechnological Engineering, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Bergeron
authors.forename: Helena
authors.initials: H
authors.lastname: Senta
authors.forename: Audrey
authors.initials: A
authors.lastname: Mailloux
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Park
authors.forename: Etienne
authors.initials: E
authors.lastname: Lord
authors.forename: Nathalie
authors.initials: N
authors.lastname: Faucheux
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D055427:Growth Differentiation Factor 2 / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: C526108:Gdf2 protein, mouse; D055427:Growth Differentiation Factor 2; D010455:Peptides