Transforming Growth Factor-β and Forskolin Increase All Classes of Insulin-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 osteoblast-like cells. Previous studies in rat osteoblastic cells have indicated that transforming growth factor-β (TGF-β) inhibits IGF-I expression, whereas inducers of intracellular cAMP stimulate IGF-I expression. However, in human osteoblast-like cells both TGF-β and forskolin increased IGF-I mRNA levels in a time- and dose-dependent manner. All 4 classes of IGF-I transcript that can result from alternate leader exon usage and splicing of the human IGF-I gene were induced proportionally. Although human osteoblasts increase IGF-I mRNA in response to important skeletal regulatory factors, some responses may be species-specific.