| First Author | Sjögren K | Year | 2002 |
| Journal | J Bone Miner Res | Volume | 17 |
| Issue | 11 | Pages | 1977-87 |
| PubMed ID | 12412805 | Mgi Jnum | J:111425 |
| Mgi Id | MGI:3653978 | Doi | 10.1359/jbmr.2002.17.11.1977 |
| Citation | Sjogren K, et al. (2002) Effects of liver-derived insulin-like growth factor I on bone metabolism in mice. J Bone Miner Res 17(11):1977-87 |
| abstractText | Insulin-like growth factor (IGF) I is an important regulator of both skeletal growth and adult bone metabolism. To better understand the relative importance of systemic IGF-I versus locally expressed IGF-I we have developed a transgenic mouse model with inducible specific IGF-I gene inactivation in the liver (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 approximately 40 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. |
