Fibroblast Growth Factor 2 Induced Proliferation in Osteoblasts and Bone Marrow Stromal Cells: A Whole Cell Model

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 modeled 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 multistep processes involved in heparan-sulfate proteoglycans-bound FGF2 release, internalization, and fragment formation in conjunction with the normal metabolism of the proteoglycan.