Fibroblast Growth Factor 2 Induced Proliferation in Osteoblasts and Bone Marrow Stromal Cells: A Whole Cell Model
Melissa A. Dupree 1, Solomon R. Pollack 1, Elliott M. Levine 2 and Cato T. Laurencin 3*
1 University of Pennsylvania
2 The Wistar Institute
3 The University of Virginia
* To whom correspondence should be addressed. E-mail: ctl3f{at}virginia.edu.
Submitted on April 12, 2006
Revised on May 26, 2006
Accepted on 30 June 2006
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Abstract |
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Fibroblast Growth Factor 2 (FGF2) can enhance the proliferative capacity of bone and bone marrow stromal cells, however, the mechanisms behind this effect are not well described. We present a whole cell kinetic model relating receptor mediated binding, internalization and processing of FGF2 to osteoblastic proliferative response. Focusing on one of the potential signaling complex stoichiometries, we utilized experimentally measured and model estimated rate constants to predict in vitro proliferation and distinguish between potential binding orders. We found that piecewise assemblage of a ternary signaling complex may occur in several ways depending on the local binding environment. Using experimental data of endocytosed FGF2 as a constraint, we have also shown evidence of potential multi-step processes involved in HSPG bound FGF2 release, internalization and fragment formation in conjunction with the normal metabolism of the proteoglycan.
Key Words:
Bone Marrow Stromal Cells, Fibroblast Growth Factor 2, Heparan Sulfate Proteoglycans, Mathematical Modeling, Osteoblast, Proliferation
