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Transgenic mice overexpressing insulin-like growth factor binding protein-5 display transiently decreased
1Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105-1299, USA.
Abstract:
Skeletal cells synthesize IGFs and their six IGF binding proteins (IGFBP). IGFBP-5 was reported to stimulate bone cell growth in vitro and selected parameters of osteoblastic function in vivo, but its actual effects on bone formation are not established. We investigated the direct effects of IGFBP-5 on bone remodeling in two lines of transgenic mice overexpressing IGFBP-5 under the control of the osteocalcin promoter. Static and dynamic histomorphometry revealed that IGFBP-5 transgenic mice had a transient decrease in trabecular bone volume secondary to reduced trabecular number and thickness and a transient decrease in bone mineral apposition rate. Osteoblast number was normal, indicating impaired osteoblastic function. Osteoclast number and bone resorption were normal. Total, vertebral, and femoral bone mineral densities were reduced in IGFBP-5 transgenics by 14-27% at 4 wk of age, but not in older animals. Stromal cells expressing the IGFBP-5 transgene displayed decreased expression of alkaline phosphatase, osteocalcin, core binding factor 1, and type I collagen transcripts when compared with cells from wild-type animals. In conclusion, transgenic mice overexpressing IGFBP-5 in the bone microenvironment have a transient decrease in trabecular bone volume, impaired osteoblastic function, and osteopenia.
Insights
Overexpressing Insulin-like Growth Factor Binding Protein-5 (IGFBP-5) in mice transiently reduced bone volume and impaired osteoblast function, leading to osteopenia. These findings suggest IGFBP-5 negatively impacts bone formation.
Area of Science:
- Biochemistry
- Cell Biology
- Bone Biology
Background:
- Skeletal cells produce Insulin-like Growth Factors (IGFs) and IGF Binding Proteins (IGFBPs).
- IGFBP-5 has shown potential to stimulate bone cell growth and osteoblastic function in vitro and in vivo.
- The precise impact of IGFBP-5 on overall bone formation remains unclear.
Purpose of the Study:
- To investigate the direct effects of IGFBP-5 overexpression on bone remodeling.
- To determine the role of IGFBP-5 in regulating osteoblastic function and bone formation.
Main Methods:
- Generation of transgenic mice overexpressing IGFBP-5 under the osteocalcin promoter.
- Utilized static and dynamic histomorphometry to analyze bone structure and turnover.
- Examined gene expression of key bone formation markers in stromal cells.
Main Results:
- IGFBP-5 transgenic mice exhibited a transient decrease in trabecular bone volume, number, and thickness.
- Bone mineral apposition rate was transiently reduced, with normal osteoblast and osteoclast numbers.
- Reduced bone mineral densities were observed in young transgenic mice, indicating impaired osteoblastic function and osteopenia.
Conclusions:
- Overexpression of IGFBP-5 in the bone microenvironment leads to a transient reduction in bone volume.
- Impaired osteoblastic function and osteopenia are consequences of IGFBP-5 overexpression.
- These findings highlight a potential negative regulatory role of IGFBP-5 in bone formation.
