Modulating osteogenesis of mesenchymal stem cells by modifying growth factor availability.
Growth factors control the proliferation and differentiation of osteoprogenitor cells. This study explores the effects of modulating growth factors (VEGF, IGF-1, FGF-2 and BMP-2) on osteogenesis of mesenchymal stem cells (MSCs) in vitro. Constant and profiled delivery protocols, in accordance with protein expression in vitro, were applied to deliver or neutralize growth factors. Cell number, alkaline phosphatase (ALP-2) and osteocalcin (OC) expression, and mineralization were measured as outcome variables. Profiled addition of VEGF increased MSC proliferation. Constant and profiled application of FGF-2 and neutralization of IGF-1 and BMP-2 decreased ALP-2 levels. Profiled addition of BMP-2 vastly increased OC release from MSCs, but constant addition of IGF-1, constant and profiled neutralization of IGF-1 and FGF-2 reduced OC levels. Constant addition of IGF-1 and FGF-2, as well as profiled loading of FGF-2 decreased mineralization of MSCs. This study indicated that endogenous IGF-1 and FGF-2 are essential to osteogenesis; excess IGF-1 and FGF-2 were inhibitory to bone formation. Selective, temporally specific addition of growth factors, such as BMP-2 and VEGF appears to be an important strategy to enhance osteogenesis.
Huang
Zhinong
Z
Orthopaedic Research Laboratory, Edwards Building R116, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, United States. Zhinong@stanford.edu
Ren
Pei-Gen
PG
Ma
Ting
T
Smith
R Lane
RL
Goodman
Stuart B
SB
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D013194:Staining and Labeling; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D057134:Antibodies, Neutralizing; D055396:Bone Morphogenetic Protein 2; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase