Serum IGF-1 affects skeletal acquisition in a temporal and compartment-specific manner

Hayden William Courtland, Sebastien Elis, Yingjie Wu, Hui Sun, Clifford J. Rosen, Karl J. Jepsen, Shoshana Yakar

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere14762
JournalPLoS One
Volume6
Issue number3
DOIs
StatePublished - 2011

Fingerprint

somatomedins
Somatomedins
Bone
bones
Serum
adulthood
Bone and Bones
mice
skeletal development
Skeleton
Bone Density
bone density
skeleton
Maintenance
Minerals
animal models
Aging of materials
Cortical Bone

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Courtland, H. W., Elis, S., Wu, Y., Sun, H., Rosen, C. J., Jepsen, K. J., & Yakar, S. (2011). Serum IGF-1 affects skeletal acquisition in a temporal and compartment-specific manner. PLoS One, 6(3), [e14762]. https://doi.org/10.1371/journal.pone.0014762

Serum IGF-1 affects skeletal acquisition in a temporal and compartment-specific manner. / Courtland, Hayden William; Elis, Sebastien; Wu, Yingjie; Sun, Hui; Rosen, Clifford J.; Jepsen, Karl J.; Yakar, Shoshana.

In: PLoS One, Vol. 6, No. 3, e14762, 2011.

Research output: Contribution to journalArticle

Courtland, Hayden William ; Elis, Sebastien ; Wu, Yingjie ; Sun, Hui ; Rosen, Clifford J. ; Jepsen, Karl J. ; Yakar, Shoshana. / Serum IGF-1 affects skeletal acquisition in a temporal and compartment-specific manner. In: PLoS One. 2011 ; Vol. 6, No. 3.
@article{ec9a5696d74a4fcca314e57a6667d53c,
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.",
author = "Courtland, {Hayden William} and Sebastien Elis and Yingjie Wu and Hui Sun and Rosen, {Clifford J.} and Jepsen, {Karl J.} and Shoshana Yakar",
year = "2011",
doi = "10.1371/journal.pone.0014762",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Serum IGF-1 affects skeletal acquisition in a temporal and compartment-specific manner

AU - Courtland, Hayden William

AU - Elis, Sebastien

AU - Wu, Yingjie

AU - Sun, Hui

AU - Rosen, Clifford J.

AU - Jepsen, Karl J.

AU - Yakar, Shoshana

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79952787715&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952787715&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0014762

DO - 10.1371/journal.pone.0014762

M3 - Article

C2 - 21445249

AN - SCOPUS:79952787715

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e14762

ER -