PMID- 12235108
OWN - NLM
STAT- MEDLINE
DCOM- 20021023
LR  - 20220409
IS  - 0021-9738 (Print)
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Linking)
VI  - 110
IP  - 6
DP  - 2002 Sep
TI  - Circulating levels of IGF-1 directly regulate bone growth and density.
PG  - 771-81
AB  - 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.
FAU - Yakar, Shoshana
AU  - Yakar S
AD  - 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.
FAU - Rosen, Clifford J
AU  - Rosen CJ
FAU - Beamer, Wesley G
AU  - Beamer WG
FAU - Ackert-Bicknell, Cheryl L
AU  - Ackert-Bicknell CL
FAU - Wu, Yiping
AU  - Wu Y
FAU - Liu, Jun-Li
AU  - Liu JL
FAU - Ooi, Guck T
AU  - Ooi GT
FAU - Setser, Jennifer
AU  - Setser J
FAU - Frystyk, Jan
AU  - Frystyk J
FAU - Boisclair, Yves R
AU  - Boisclair YR
FAU - LeRoith, Derek
AU  - LeRoith D
LA  - eng
GR  - R01 DK051624/DK/NIDDK NIH HHS/United States
GR  - DK-51624/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Carrier Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Insulin-Like Growth Factor Binding Proteins)
RN  - 0 (insulin-like growth factor binding protein, acid labile subunit)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9002-72-6 (Growth Hormone)
SB  - IM
MH  - Animals
MH  - Bone Density/*physiology
MH  - Bone Development/*physiology
MH  - Carrier Proteins/*genetics/metabolism
MH  - Glycoproteins/*genetics/metabolism
MH  - Growth Hormone/blood
MH  - Insulin-Like Growth Factor Binding Proteins/blood
MH  - Insulin-Like Growth Factor I/genetics/*metabolism
MH  - Liver/metabolism
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Tibia/cytology/metabolism
PMC - PMC151128
EDAT- 2002/09/18 10:00
MHDA- 2002/10/31 04:00
PMCR- 2002/09/15
CRDT- 2002/09/18 10:00
PHST- 2002/09/18 10:00 [pubmed]
PHST- 2002/10/31 04:00 [medline]
PHST- 2002/09/18 10:00 [entrez]
PHST- 2002/09/15 00:00 [pmc-release]
AID - 15463 [pii]
AID - 10.1172/JCI15463 [doi]
PST - ppublish
SO  - J Clin Invest. 2002 Sep;110(6):771-81. doi: 10.1172/JCI15463.