Effects of liver-derived insulin-like growth factor I on bone metabolism in mice.
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.
Sjögren
Klara
K
RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
Sheng
Matilda
M
Movérare
Sofia
S
Liu
Jun-Li
JL
Wallenius
Kristina
K
Törnell
Jan
J
Isaksson
Olle
O
Jansson
John-Olov
JO
Mohan
Subburaman
S
Ohlsson
Claes
C
D015502:Absorptiometry, Photon; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density; D001846:Bone Development / Q000235:genetics; D001862:Bone Resorption; D001842:Bone and Bones / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism*; D008099:Liver / Q000502:physiology*; D019563:Mechanics; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity
D015415:Biomarkers; D007334:Insulin-Like Growth Factor I