title: Serum IGF-1 affects skeletal acquisition in a temporal and compartment-specific manner.
abstract: Insulin-like growth factor-1 (IGF-1) plays a critical role in the development of the growing skeleton by establishing both longitudinal and transverse bone accrual. IGF-1 has also been implicated in the maintenance of bone mass during late adulthood and aging, as decreases in serum IGF-1 levels appear to correlate with decreases in bone mineral density (BMD). Although informative, mouse models to date have been unable to separate the temporal effects of IGF-1 depletion on skeletal development. To address this problem, we performed a skeletal characterization of the inducible LID mouse (iLID), in which serum IGF-1 levels are depleted at selected ages. We found that depletion of serum IGF-1 in male iLID mice prior to adulthood (4 weeks) decreased trabecular bone architecture and significantly reduced transverse cortical bone properties (Ct.Ar, Ct.Th) by 16 weeks (adulthood). Likewise, depletion of serum IGF-1 in iLID males at 8 weeks of age, resulted in significantly reduced transverse cortical bone properties (Ct.Ar, Ct.Th) by 32 weeks (late adulthood), but had no effect on trabecular bone architecture. In contrast, depletion of serum IGF-1 after peak bone acquisition (at 16 weeks) resulted in enhancement of trabecular bone architecture, but no significant changes in cortical bone properties by 32 weeks as compared to controls. These results indicate that while serum IGF-1 is essential for bone accrual during the postnatal growth phase, depletion of IGF-1 after peak bone acquisition (16 weeks) is compartment-specific and does not have a detrimental effect on cortical bone mass in the older adult mouse.
authors: Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, New York, United States of America.
authors: Hayden-William
authors: HW
authors: Courtland
authors: Sebastien
authors: S
authors: Elis
authors: Yingjie
authors: Y
authors: Wu
authors: Hui
authors: H
authors: Sun
authors: Clifford J
authors: CJ
authors: Rosen
authors: Karl J
authors: KJ
authors: Jepsen
authors: Shoshana
authors: S
authors: Yakar
mesh_terms: D000375:Aging; D000818:Animals; D015519:Bone Density; D001846:Bone Development; D020869:Gene Expression Profiling; D013006:Growth Hormone / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D014057:Tomography, X-Ray Computed
chemical_list: D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone