Elevated serum IGF-1 levels synergize PTH action on the skeleton only when the tissue IGF-1 axis is intact

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

Research output: Contribution to journalArticle

Abstract

There is growing evidence that insulin-like growth factor 1 (IGF-1) and parathyroid hormone (PTH) have synergistic actions on bone and that part of the anabolic effects of PTH is mediated by local production of IGF-1. In this study we analyzed the skeletal response to PTH in mouse models with manipulated endocrine or autocrine/paracrine IGF-1. We used mice carrying a hepatic IGF-1 transgene (HIT), which results in a threefold increase in serum IGF-1 levels and normal tissue IGF-1 expression, and Igf1 null mice with blunted IGF-1 expression in tissues but threefold increases in serum IGF-1 levels (KO-HIT). Evaluation of skeletal growth showed that elevations in serum IGF-1 in mice with Igf1 gene ablation in all tissues except the liver (KO-HIT) resulted in a restoration of skeletal morphology and mechanical properties by adulthood. Intermittent PTH treatment of adult HIT mice resulted in increases in serum osteocalcin levels, femoral total cross-sectional area, cortical bone area and cortical bone thickness, as well as bone mechanical properties. We found that the skeletal response of HIT mice to PTH was significantly higher than that of control mice, suggesting synergy between IGF-1 and PTH on bone. In sharp contrast, although PTH-treated KO-HIT mice demonstrated an anabolic response in cortical and trabecular bone compartments compared with vehicle-treated KO-HIT mice, their response was identical to that of PTH-treated control mice. We conclude that (1) in the presence of elevated serum IGF-1 levels, PTH can exert an anabolic response in bone even in the total absence of tissue IGF-1, and (2) elevations in serum IGF-1 levels synergize PTH action on bone only if the tissue IGF-1 axis is intact. Thus enhancement of PTH anabolic actions depends on tissue IGF-1.

Original languageEnglish (US)
Pages (from-to)2051-2058
Number of pages8
JournalJournal of Bone and Mineral Research
Volume25
Issue number9
DOIs
StatePublished - Sep 2010

Fingerprint

Somatomedins
Parathyroid Hormone
Skeleton
Serum
Transgenes
Insulin-Like Growth Factor I
Liver
Bone and Bones
Anabolic Agents
Osteocalcin
Thigh

Keywords

  • Bone
  • Endocrine IGF-1
  • IGF-1
  • IGF1KO
  • Intermittent PTH
  • Micro-Computed Tomography
  • Transgenic Mice

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Elevated serum IGF-1 levels synergize PTH action on the skeleton only when the tissue IGF-1 axis is intact. / Elis, Sebastien; Courtland, Hayden William; Wu, Yingjie; Fritton, J. Christopher; Sun, Hui; Rosen, Clifford J.; Yakar, Shoshana.

In: Journal of Bone and Mineral Research, Vol. 25, No. 9, 09.2010, p. 2051-2058.

Research output: Contribution to journalArticle

Elis, Sebastien ; Courtland, Hayden William ; Wu, Yingjie ; Fritton, J. Christopher ; Sun, Hui ; Rosen, Clifford J. ; Yakar, Shoshana. / Elevated serum IGF-1 levels synergize PTH action on the skeleton only when the tissue IGF-1 axis is intact. In: Journal of Bone and Mineral Research. 2010 ; Vol. 25, No. 9. pp. 2051-2058.
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