Conditional Deletion of Insulin-Like Growth Factor-I in Collagen Type 1{alpha}2-Expressing Cells Results in Postnatal Lethality and a Dramatic Reduction in Bone Accretion.

Conditional Deletion of Insulin-Like Growth Factor-I in Collagen Type 1{alpha}2-Expressing Cells Results in Postnatal Lethality and a Dramatic Reduction in Bone Accretion. Research Abstract Details 

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Conditional Deletion of Insulin-Like Growth Factor-I in Collagen Type 1{alpha}2-Expressing Cells Results in Postnatal Lethality and a Dramatic Reduction in Bone Accretion. Abstract Text:

Kristen E Govoni,Jon E Wergedal,Lore Florin,Peter Angel,David J Baylink,Subburaman Mohan,Kristen E Govoni,Jon E Wergedal,Lore Florin,Peter Angel,David J Baylink,Subburaman Mohan,

IGF-I acts through endocrine and local, autocrine/paracrine routes. Disruption of both endocrine and local IGF-I action leads to neonatal lethality and impaired growth in various tissues including bone; however, the severity of growth and skeletal phenotype caused by disruption of endocrine IGF-I action is far less than with total IGF-I disruption. Based on these data and the fact that bone cells express IGF-I in high abundance, we and others predicted that locally produced IGF-I is also critical in regulating growth and bone accretion. To determine the role of local IGF-I, type 1alpha2 collagen-Cre mice were crossed with IGF-I loxP mice to generate Cre+ (conditional mutant) and Cre- (control) loxP homozygous mice. Surprisingly, approximately 40-50% of the conditional mutants died at birth, which is similar to total IGF-I disruption, but not observed in mice lacking circulating IGF-I. Expression of IGF-I in bone and muscle but not liver and brain was significantly decreased in the conditional mutant. Accordingly, circulating levels of serum IGF-I were also not affected. Disruption of local IGF-I dramatically reduced body weight 28-37%, femur areal bone mineral density 10-25%, and femur bone size 18-24% in growing mice. In addition, mineralization was reduced as early as during embryonic development. Consistently, histomorphometric analysis determined impaired osteoblast function as demonstrated by reduced mineral apposition rate (14-30%) and bone formation rate (35-57%). In conclusion, both local and endocrine IGF-I actions are involved in regulating growth of various tissues including bone, but they act via different mechanisms.

Conditional Deletion of Insulin-Like Growth Factor-I in Collagen Type 1{alpha}2-Expressing Cells Results in Postnatal Lethality and a Dramatic Reduction in Bone Accretion. Publishing Authors By Initials

KE Govoni,JE Wergedal,L Florin,P Angel,DJ Baylink,S Mohan,KE Govoni,JE Wergedal,L Florin,P Angel,DJ Baylink,S Mohan,

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Conditional Deletion of Insulin-Like Growth Factor-I in Collagen Type 1{alpha}2-Expressing Cells Results in Postnatal Lethality and a Dramatic Reduction in Bone Accretion. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Endocrinology

VOLUME: 148

Page Numbers: 5706-15

Journal Abbreviation: Endocrinology

ISSN: 0013-7227

DAY: 23

MONTH: 08

YEAR: 2007

Conditional Deletion of Insulin-Like Growth Factor-I in Collagen Type 1{alpha}2-Expressing Cells Results in Postnatal Lethality and a Dramatic Reduction in Bone Accretion. Information

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LANGUAGE: eng

NlmUniqueID: 375040

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Grant and Affiliation Information for Conditional Deletion of Insulin-Like Growth Factor-I in Collagen Type 1{alpha}2-Expressing Cells Results in Postnatal Lethality and a Dramatic Reduction in Bone Accretion.

AFFILIATION: Musculoskeletal Disease Center (151), Jerry L. Pettis Memorial Veterans Affairs Medical Center, 11201 Benton Street, Loma Linda, California 92357. subburaman.mohan@va.gov.

Country: United States

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MEDLINETA: Endocrinology

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