[Autocrine regulation of cell proliferation and secretion of insulin-like growth factor I (IGF-I) in osteoblastic cell line MC3T3-E1].

Bone cells maintained in culture produce different growth factors which modulate cell growth via a mechanism of auto/paracrine regulation. IGF-1 is abundantly produced by murine bone cells where it acts as a mitogenic agent. The aim of this work was to study the effect of IGF-II, TGF beta 1, basic FGF (FGFb) and PDGF on cell growth and production of IGF-1 in the murine osteoblastic clonal cell line MC3T3-E1. IGF-1 was assayed by RIA after elimination of the IGF binding proteins. After 24th of treatment in culture conditions without serum, incorporation of [3H] methylthymidine increased significantly in MC3T3-E1 treated with IGF-II, FGFb and PDGF. The effect was dose-dependent. At low cell density (2.5 X 10(4) cemm/cm2) and after 24 h treatment, IGF-II at 10 ng/ml led to a 220% increase in IGF-I production in MC3T3-E1 cells (9.5 +/- 1.5 vs 4.2 +/- 0.44 ng/micrograms protein, p < 0.001) while TGF beta 1, FGFb and PDGF at 1 ng/ml led to a significant decrease (65, 95 and 85% respectively) in IGF-I (TGF beta 1: 1.5 +/- 0.3 ng/micrograms; FGBb: 0.21 +/- 0.04 ng/micrograms; PDGF: 0.66 +/- 0.1 ng/micrograms; p < 0.001). Production of IGF-I was controlled by a dose-dependent relationship and varied as a function of incubation time and cell density. IGF-II led to an increase in mRNA coding for IGF-1 as early as the first hour after IGF-II addition with a maximal effect at 6 hours.(ABSTRACT TRUNCATED AT 250 WORDS)