Endocrine Abstracts

Background: Dexamethasone (Dex) induced growth retardation in children is partly mediated by direct growth plate effects. In contrast, IGF-I induces bone growth and may ameliorate these effects.
Aims: To determine the direct effects of Dex and IGF-I on bone length, cell proliferation and mineralisation in cultured fetal mouse metatarsals.
Methods: 18-day-old fetal metatarsals were cultured in triplicate in serum-free medium for 12 days supplemented with either Dex 10^-4M, IGF-I (100ng/ml) or both. Total metatarsal and mineralisation zone growth was determined as a percent change from their initial length at day 0. Dry weight and [3H]-thymidine uptake (dpm/mg dry weight) were determined on day 12.
Results: Dex caused a decrease in length of 22% and IGF-I an increase of 23% compared to the control bones (p<0.05), which increased by 84% over the 12 day period. Dex had no effect on dry weight, whereas IGF-I treated bones were significantly heavier (152ug +/- 5) than control (84ug +/- 2: p<0.05). The mineralising zone (MZ) length increased with all treatments, but this was significantly lower with Dex at day 12 and IGF-I from day 8 compared to the controls (p<0.05). Cell proliferation was significantly reduced with Dex 10^-4M (p<0.05), which may explain the reduced linear growth. Interestingly, IGF-I also caused a decrease in proliferation (p<0.05), which possibly reflected the slowing of growth at day 12 compared to the controls. There were no significant differences in the width of the MZ. The combined effects of Dex and IGF-I were intermediate on all parameters.
Conclusion: The results indicate that Dex and IGF-I have opposite effects on longitudinal bone growth. Dex reduces bone length whereas IGF-I promotes linear growth in favour of mineralisation. This system represents a good physiological model for growth plate studies and will be invaluable for the study of glucocorticoid induced growth retardation.