TRANSFORMING GROWTH-FACTOR-BETA AND FORSKOLIN INCREASE ALL CLASSES OFINSULIN-LIKE GROWTH-FACTOR-I TRANSCRIPTS IN NORMAL HUMAN OSTEOBLAST-LIKE CELLS

In this study, we examined regulation of insulin-like growth factor I (IGF-I) gene expression and transcript splicing in normal human osteob last-like cells. Previous studies in rat osteoblastic cells have indic ated that transforming growth factor-beta (TGF-beta) inhibits IGF-I ex pression, whereas inducers of intracellular cAMP stimulate IGF-I expre ssion. However, in human osteoblast-like cells both TGF-beta and forsk olin increased IGF-I mRNA levels in a time-and dose-dependent manner. All 4 classes of IGF-I transcript that can result from alternate leade r exon usage and splicing of the human IGF-I gene were induced proport ionally. Although human osteoblasts increase IGF-I mRNA in response to important skeletal regulatory factors, some responses may be species- specific. (C) 1995 Academic Press, Inc.