Circulating levels of IGF-1 directly regulate bone growth and density
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...
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Published in | The Journal of clinical investigation Vol. 110; no. 6; pp. 771 - 781 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Clinical Investigation
01.09.2002
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Subjects | |
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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. |
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AbstractList | 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. |
Author | Liu, Jun-Li Setser, Jennifer Ackert-Bicknell, Cheryl L Wu, Yiping Beamer, Wesley G Ooi, Guck T Frystyk, Jan Boisclair, Yves R LeRoith, Derek Rosen, Clifford J Yakar, Shoshana |
Author_xml | – sequence: 1 givenname: Shoshana surname: Yakar fullname: Yakar, Shoshana organization: Section 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 – sequence: 2 givenname: Clifford J surname: Rosen fullname: Rosen, Clifford J – sequence: 3 givenname: Wesley G surname: Beamer fullname: Beamer, Wesley G – sequence: 4 givenname: Cheryl L surname: Ackert-Bicknell fullname: Ackert-Bicknell, Cheryl L – sequence: 5 givenname: Yiping surname: Wu fullname: Wu, Yiping – sequence: 6 givenname: Jun-Li surname: Liu fullname: Liu, Jun-Li – sequence: 7 givenname: Guck T surname: Ooi fullname: Ooi, Guck T – sequence: 8 givenname: Jennifer surname: Setser fullname: Setser, Jennifer – sequence: 9 givenname: Jan surname: Frystyk fullname: Frystyk, Jan – sequence: 10 givenname: Yves R surname: Boisclair fullname: Boisclair, Yves R – sequence: 11 givenname: Derek surname: LeRoith fullname: LeRoith, Derek |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/12235108$$D View this record in MEDLINE/PubMed |
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Snippet | 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... |
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SubjectTerms | Acids Animals Biomedical research Bone density Bone Density - physiology Bone Development - physiology Carrier Proteins - genetics Carrier Proteins - metabolism Glycoproteins - genetics Glycoproteins - metabolism Growth Hormone - blood Growth hormones Insulin-Like Growth Factor Binding Proteins - blood Insulin-Like Growth Factor I - genetics Insulin-Like Growth Factor I - metabolism Liver Liver - metabolism Mice Mice, Inbred Strains Mice, Knockout Proteins Roles Tibia - cytology Tibia - metabolism |
Title | Circulating levels of IGF-1 directly regulate bone growth and density |
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