Synergistic effects of dexamethasone on platelet-derived growth factor mitogenesis in vitro

Abstract

Platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) interact to stimulate proliferation of fibroblasts in culture. Glucocorticoids variably effect the response of cultured fibroblasts to polypeptide growth factors. This study determined the effects of dexamethasone on growthfactor stimulation of gingival, periodontal ligament and pulp fibroblast proliferation in vitro. Cultures of quiescent, low-passage, human fibroblasts were treated for varying periods of time with transforming growth factor- β 2 (TGF- β 2), PDGF and IGF-I: (1) alone, (2) in combination with each other, (3) singly plus dexamethasone, (4) in combination plus dexamethasone. Combinations of human, recombinant PDGF and IGF-I (10–1000 ng/ml) induced significantly higher rates of cell proliferation than either factor alone. Dexamethasone at doses ranging from 10 −5 to 10 −8 M substantially enhanced cell proliferation induced by these combinations and by PDGF without IGF-I but not IGF-I alone. By 6 days after a single application, 2–3 times as many cells were present in the PDGF and dexamethasone cultures as compared to PDGF without IGF-I. TGF- β 2 specifically blocked the effects of dexamethasone added to PDGF-stimulated cells. Collagen and non-collagenous protein synthesis was not affected by the addition of PDGF and IGF-I with or without dexamethasone. These data suggest that dexamethasone may substitute for IGF-I in PDGF stimulation of cell proliferation.