The skeletal structure of insulin-like growth factor I-deficient mice.
The importance of insulin-like growth factor I (IGF-I) for growth is well established. However, the lack of IGF-I on the skeleton has not been examined thoroughly. Therefore, we analyzed the structural properties of bone from mice rendered IGF-I deficient by homologous recombination (knockout [k/o]) using histomorphometry, peripheral quantitative computerized tomography (pQCT), and microcomputerized tomography (muCT). The k/o mice were 24% the size of their wild-type littermates at the time of study (4 months). The k/o tibias were 28% and L1 vertebrae were 26% the size of wild-type bones. Bone formation rates (BFR) of k/o tibias were 27% that of the wild-type littermates. The k/o bones responded normally to growth hormone (GH; 1.7-fold increase) and supranormally to IGF-I (5.2-fold increase) with respect to BFR. Cortical thickness of the proximal tibia was reduced 17% in the k/o mouse. However, trabecular bone volume (bone volume/total volume [BV/TV]) was increased 23% (male mice) and 88% (female mice) in the k/o mice compared with wild-type controls as a result of increased connectivity, increased number, and decreased spacing of the trabeculae. These changes were either less or not found in L1. Thus, lack of IGF-I leads to the development of a bone structure, which, although smaller, appears more compact.
Bikle
D
D
Department of Medicine, University of California and Veterans Affairs Medical Center, San Francisco 94121, USA.
Majumdar
S
S
Laib
A
A
Powell-Braxton
L
L
Rosen
C
C
Beamer
W
W
Nauman
E
E
Leary
C
C
Halloran
B
B
D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis; D012737:Sex Factors; D013977:Tibia / Q000503:physiopathology
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone