Forschungsdatenbank PMU-SQQUID

PMU-Autor/inn/en

Abstract

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 micro CT. A strong linear relationship was found between DXA and ash weight, and between pQCT and muCT (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.

Useful keywords (using NLM MeSH Indexing)

Absorptiometry, Photon

Animals

Bone Density

Bone and Bones/metabolism*

Bone and Bones/pathology

Bone and Bones/radiography

Gene Expression Regulation, Developmental

Heterozygote

Insulin-Like Growth Factor Binding Protein 2/genetics

Insulin-Like Growth Factor Binding Protein 2/metabolism*

Insulin-Like Growth Factor I/genetics*

Insulin-Like Growth Factor I/metabolism

Male

Mice

Mice, Transgenic

Osteogenesis/drug effects

Osteogenesis/genetics*

Tomography, X-Ray Computed

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