Circulating levels of IGF-1 directly regulate bone growth and density

Shoshana Yakar, Clifford J. Rosen, Wesley G. Beamer, Cheryl L. Ackert-Bicknell, Yiping Wu, Jun Li Liu, Guck T. Ooi, Jennifer Setser, Jan Frystyk, Yves R. Boisclair, Derek LeRoith

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)771-781
Number of pages11
JournalJournal of Clinical Investigation
Volume110
Issue number6
DOIs
StatePublished - Sep 2002

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Bone Development
Insulin-Like Growth Factor I
Bone Density
Knockout Mice
Insulin-Like Growth Factor Binding Protein 3
Growth Plate
Liver
Serum
Tibia
Growth and Development
Acids
Chondrocytes
Growth
Genes
Osteoporosis
Half-Life
Peptides

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Yakar, S., Rosen, C. J., Beamer, W. G., Ackert-Bicknell, C. L., Wu, Y., Liu, J. L., ... LeRoith, D. (2002). Circulating levels of IGF-1 directly regulate bone growth and density. Journal of Clinical Investigation, 110(6), 771-781. https://doi.org/10.1172/JCI200215463

Circulating levels of IGF-1 directly regulate bone growth and density. / Yakar, Shoshana; Rosen, Clifford J.; Beamer, Wesley G.; Ackert-Bicknell, Cheryl L.; Wu, Yiping; Liu, Jun Li; Ooi, Guck T.; Setser, Jennifer; Frystyk, Jan; Boisclair, Yves R.; LeRoith, Derek.

In: Journal of Clinical Investigation, Vol. 110, No. 6, 09.2002, p. 771-781.

Research output: Contribution to journalArticle

Yakar, S, Rosen, CJ, Beamer, WG, Ackert-Bicknell, CL, Wu, Y, Liu, JL, Ooi, GT, Setser, J, Frystyk, J, Boisclair, YR & LeRoith, D 2002, 'Circulating levels of IGF-1 directly regulate bone growth and density', Journal of Clinical Investigation, vol. 110, no. 6, pp. 771-781. https://doi.org/10.1172/JCI200215463
Yakar, Shoshana ; Rosen, Clifford J. ; Beamer, Wesley G. ; Ackert-Bicknell, Cheryl L. ; Wu, Yiping ; Liu, Jun Li ; Ooi, Guck T. ; Setser, Jennifer ; Frystyk, Jan ; Boisclair, Yves R. ; LeRoith, Derek. / Circulating levels of IGF-1 directly regulate bone growth and density. In: Journal of Clinical Investigation. 2002 ; Vol. 110, No. 6. pp. 771-781.
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