GROWTH-FACTORS REGULATE THE SYNTHESIS OF INSULIN-LIKE GROWTH FACTOR-IIN BONE CELL-CULTURES

Insulin-like growth factor-I (IGF-I), a prevalent growth factor secret ed by bone cells, has important effects on bone remodeling. Hormones a re known to regulate the synthesis of skeletal IGF-I, but there is lim ited information about the actions of growth factors on IGF-I synthesi s. We tested the effects of basic fibroblast growth factor (bFGF), tra nsforming growth factor-beta1 (TGFbeta1), and platelet-derived growth factors (PDGF) AA and BB on IGF-I mRNA expression and polypeptide conc entrations in cultures of osteoblast-enriched (Ob) cells from 22-day-o ld fetal rat calvariae. Steady state IGF-I mRNA levels were determined by Northern blot analysis, and IGF-I concentrations were determined i n acidified and fractionated culture medium by a specific RIA. Treatme nt of Ob cells with bFGF at 0.06-6 nM, TGFbeta1 at 0.04-4 nM, and PDGF BB at 0.3-3.3 nM caused a dose-dependent decrease in steady state IGF -I MRNA. A smaller effect was observed with PDGF AA. The effect was in itially observed after 6-8 h of treatment and was maximal after 16 h. Treatment with bFGF at 0.6-6 nM, TGFbeta1 at 0.4-4 nM, and PDGF BB at 0.3-3.3 nM for 24 h decreased IGF-I polypeptide concentrations by 40-8 0%. The effects of bFGF, TGFbeta1, and PDGF BB and AA on IGF-I mRNA we re independent of protein synthesis and cell division, as they were ob served in the presence and absence of cycloheximide at 3.6 muM or hydr oxyurea at 1 mM. Similarly, their inhibitory actions on immunoreactive IGF-I were not prevented by hydroxyurea. In conclusion, bFGF, TGFbeta 1, PDGF BB, and, to a lesser extent, PDGF AA decrease skeletal IGF-I s ynthesis by reducing IGF-I transcript levels, and this effect may cont ribute to their actions on selected aspects of Ob cell function.