Modulating osteogenesis of mesenchymal stem cells by modifying growth factor availability

被引:132
作者
Huang, Zhinong [1 ]
Ren, Pei-Gen [1 ]
Ma, Ting [1 ]
Smith, R. Lane [1 ]
Goodman, Stuart B. [1 ]
机构
[1] Stanford Univ, Med Ctr, Orthopaed Res Lab, Stanford, CA 94305 USA
关键词
Mesenchymal stem cell; Bone morphogenetic protein; Insulin-like growth factor; Fibroblast growth factor basic; Vascular endothelial growth factor; FACTOR-I; OSTEOBLASTIC DIFFERENTIATION; GENE-EXPRESSION; BONE TURNOVER; STROMAL CELLS; PROTEIN-1; PROLIFERATION; INSULIN-LIKE-GROWTH-FACTOR-1; RECEPTOR; ANGIOGENESIS;
D O I
10.1016/j.cyto.2010.06.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:305 / 310
页数:6
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