Circulating levels of IGF-1 directly regulate bone growth and density.
Document Type
Article
Publication Date
2002
Keywords
Bone-Development, Carrier-Proteins, Glycoproteins, Growth-Hormone, Insulin-Like-Growth-Factor-I, Insulin-Like-Growth-Factor-Binding-Proteins, Liver, Mice, Mice-Inbred-Strains, Mice-Knockout, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Tibia
First Page
771
Last Page
781
JAX Source
J Clin Invest 2002 Sep;110(6):771-81.
Abstract
IGF-1 is a growth-promoting polypeptide that is essential for normal growth and development. In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS). This complex prolongs the half-life of serum IGFs and facilitates their endocrine actions. Liver IGF-1-deficient (LID) mice and ALS knockout (ALSKO) mice exhibited relatively normal growth and development, despite having 75% and 65% reductions in serum IGF-1 levels, respectively. Double gene disrupted mice were generated by crossing LID+ALSKO mice. These mice exhibited further reductions in serum IGF-1 levels and a significant reduction in linear growth. The proximal growth plates of the tibiae of LID+ALSKO mice were smaller in total height as well as in the height of the proliferative and hypertrophic zones of chondrocytes. There was also a 10% decrease in bone mineral density and a greater than 35% decrease in periosteal circumference and cortical thickness in these mice. IGF-1 treatment for 4 weeks restored the total height of the proximal growth plate of the tibia. Thus, the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis.
Recommended Citation
Yakar S,
Rosen CJ,
Beamer WG,
Ackert BC,
Wu Y,
Liu JL,
Ooi GT,
Setser J,
Frystyk J,
Boisclair YR,
LeRoith D.
Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest 2002 Sep;110(6):771-81.