Insulin-like growth factor-binding protein-2 (IGFBP-2) overexpression negatively regulates bone size and mass, but not density, in the absence and presence of growth hormone/IGF-I excess in transgenic mice.
Insulin-like growth factor-binding protein-2 (IGFBP-2) has been suggested to be a negative regulator of bone growth and maintenance. The objective of this study was to characterize the effect of elevated IGFBP-2 on the skeletal phenotype of adult transgenic mice, in the absence and presence of growth hormone (GH) excess. 43 male mice were examined at an age of 4 months (7 IGFBP-2 transgenic mice, 12 GH transgenic mice, 10 mice carrying both transgenes, and 14 controls). The bone mineral content of the total skeleton and of isolated bones was quantified by dual energy X-ray absorptiometry (DXA), after validation versus ash analysis. Cortical and trabecular bone was quantified by peripheral quantitative computed tomography (pQCT), after validation versus microCT. A strong linear relationship was found between DXA and ash weight, and between pQCT and micro CT ( r>0.95). Bone size and bone mineral content were significantly reduced in IGFBP-2 transgenic mice, the magnitude of the effect varying between skeletal sites and between bone compartments. Elevated IGFBP-2 negatively modulated the GH-stimulated increase in bone size and mineral content, and completely blocked GH-effects at cortical sites. Notably, bone density was not decreased in IGFBP-2 transgenic animals compared with controls. In conclusion, IGFBP-2 is identified as a potent negative regulator of normal and GH-stimulated bone growth in vivo. Interestingly, elevated IGFBP-2 levels did not lead to a decrease in bone density, suggesting that IGFBP-2 negatively affects bone size and mineral content, but not bone maintenance in adult mice.
Eckstein
Felix
F
Forschungsgruppe Muskuloskelettales System, Anatomische Anstalt, Ludwig-Maximilians-Universität München, Pettenkoferstrasse 11, 80336 München, Germany. eckstein@anat.med.uni-muenchen.de
Pavicic
Tatjana
T
Nedbal
Sabine
S
Schmidt
Corina
C
Wehr
Ulrich
U
Rambeck
Walter
W
Wolf
Eckhard
E
Hoeflich
Andreas
A
D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics*; D014057:Tomography, X-Ray Computed
D018971:Insulin-Like Growth Factor Binding Protein 2; D007334:Insulin-Like Growth Factor I