Identification of a Growth Factor Mimicking the Synergistic Effect of Fetal Bovine Serum on BMP-9 Cell Response

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...

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Published in:Tissue engineering. Part A 2014-09, Vol.20 (17-18), p.2524-2535
Main Authors: Lauzon, Marc-Antoine, Daviau, Alex, Drevelle, Olivier, Marcos, Bernard, Faucheux, Nathalie
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Bones
Cattle
Cell Differentiation - drug effects
Cell Differentiation - physiology
Cellular biology
Drug Synergism
Growth Differentiation Factors - pharmacology
Humans
Intercellular Signaling Peptides and Proteins - metabolism
Mice
Original Articles
Osteoblasts - cytology
Osteoblasts - drug effects
Osteoblasts - metabolism
Osteogenesis - drug effects
Osteogenesis - physiology
Proteins
Recombinant Proteins
Serum - metabolism
Signal transduction
Tissue engineering
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Summary: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 EC 50 of BMP-9 fourfold to sixfold, as determined by osterix gene expression and alkaline phosphatase (ALP) activity, while it had no influence on EC 50 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.
ISSN:1937-3341
1937-335X
DOI:10.1089/ten.tea.2014.0091