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Circulating levels of IGF-1 directly regulate bone growth and density
Shoshana Yakar1, Clifford J Rosen, Wesley G Beamer
1Section on Cellular and Molecular Physiology, Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland 20892, USA.
The Journal of Clinical Investigation
|September 18, 2002
Summary
A threshold of Insulin-like Growth Factor 1 (IGF-1) is crucial for bone growth. Reduced IGF-1 levels in mice impaired growth plate development and bone density, highlighting IGF-1
Area of Science:
- Endocrinology
- Bone Biology
- Genetics
Background:
- Insulin-like Growth Factor 1 (IGF-1) is vital for growth and development.
- IGF-1 circulates in a complex with IGF binding protein 3 (IGFBP-3) and the acid labile subunit (ALS), which extends its half-life.
- Liver IGF-1-deficient (LID) and ALS knockout (ALSKO) mice show manageable growth despite reduced IGF-1.
Purpose of the Study:
- To investigate the combined effects of liver-specific IGF-1 deficiency and ALS deficiency on bone growth.
- To establish a mouse model for studying the role of circulating IGF-1 levels in bone development and osteoporosis.
Main Methods:
- Generation of double gene-disrupted mice by crossing LID and ALSKO mouse lines.
- Analysis of serum IGF-1 levels, linear growth, and bone morphology (growth plate dimensions, bone mineral density, cortical thickness).
- Assessment of IGF-1 treatment effects on bone growth in the double knockout model.
Main Results:
- Double gene disruption (LID+ALSKO) led to further decreased serum IGF-1 and significantly reduced linear growth.
- Proximal tibial growth plates were smaller, with reduced proliferative and hypertrophic zones in LID+ALSKO mice.
- Bone mineral density, periosteal circumference, and cortical thickness were significantly decreased in LID+ALSKO mice.
Conclusions:
- A threshold concentration of circulating IGF-1 is essential for normal bone growth.
- The IGF-1/IGFBP-3/ALS axis plays a critical role in bone development.
- This mouse model provides insights into the pathophysiology of osteoporosis related to IGF-1 deficiency.
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