title: Identification of a growth factor mimicking the synergistic effect of fetal bovine serum on BMP-9 cell response.
abstract: The bone morphogenetic proteins (BMPs) are potent osteogenic molecules that are used for bone repair in delivery systems and in regenerative medicine. We studied the responses of murine MC3T3-E1 preosteoblasts to doses of recombinant human (rh)BMP-9 with and without fetal bovine serum (FBS). rhBMP-2 was used as a control since it is currently approved by the Food and Drug Administration for bone application. We analyzed the major cell signaling pathways and the expression of osteogenic markers. Without FBS, BMP-9 had a similar effect on MC3T3-E1 preosteoblast differentiation in comparison to BMP-2. In contrast, FBS reduced the EC50 of BMP-9 fourfold to sixfold, as determined by osterix gene expression and alkaline phosphatase (ALP) activity, while it had no influence on EC50 of BMP-2. As suggested by MAPK inhibitor assays, FBS could induce an intracellular signaling environment that favors cell response to BMP-9 by inhibiting ERK1/2 activation and increasing p38 phosphorylation. Finally, IGF-2 (100 ng/mL) could mimic the effect of FBS on BMP-9 cell response in terms of MAPK signaling and ALP activity. Thus, the action of BMP-9 on preosteoblast differentiation can be greatly improved by IGF-2. This finding may well be critical for developing optimal growth factor delivery systems and bone tissue engineering strategies.
authors.affiliation: 1 Canada Research Chair on Cell-Biomaterial Biohybrid Systems, Université de Sherbrooke , Sherbrooke, Canada .
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Lauzon
authors.forename: Alex
authors.initials: A
authors.lastname: Daviau
authors.forename: Olivier
authors.initials: O
authors.lastname: Drevelle
authors.forename: Bernard
authors.initials: B
authors.lastname: Marcos
authors.forename: Nathalie
authors.initials: N
authors.lastname: Faucheux
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins; D044967:Serum / Q000378:metabolism*
chemical_list: C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins