Effects of Liver-Derived Insulin-Like Growth Factor I on Bone Metabolism in Mice (original) (raw)

2002, Journal of Bone and Mineral Research

(LI-IGF-I ؊/؊ ). These mice are growing normally up to 12 weeks of age but have a disturbed carbohydrate and lipid metabolism. In this study, the long-term effects of liver-specific IGF-I inactivation on skeletal growth and adult bone metabolism were investigated. The adult (week 8 -55) axial skeletal growth was decreased by 24% in the LI-IGF-I ؊/؊ mice whereas no major reduction of the adult appendicular skeletal growth was seen. The cortical cross-sectional bone area, as measured in the middiaphyseal region of the long bones, was decreased in old LI-IGF-I ؊/؊ mice. This reduction in the amount of cortical bone was caused mainly by decreased periosteal circumference and was associated with a weaker bone determined by a decrease in ultimate load. In contrast, the amount of trabecular bone was not decreased in the LI-IGF-I ؊/؊ mice. DNA microarray analysis of 30-week-old LI-IGF-I ؊/؊ and control mice indicated that only four genes were regulated in bone whereas ϳ40 genes were regulated in the liver, supporting the hypothesis that liver-derived IGF-I is of minor importance for adult bone metabolism. In summary, liver-derived IGF-I exerts a small but significant effect on cortical periosteal bone growth and on adult axial skeletal growth while it is not required for the maintenance of the trabecular bone in adult mice. (J Bone Miner Res 2002;17:1977

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