RAGE supports parathyroid hormone-induced gains in femoral trabecular bone

Binu K. Philip, Paul J. Childress, Alexander G. Robling, Aaron Heller, Peter P. Nawroth, Angelika Bierhaus, Joseph P. Bidwell

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Parathyroid hormone (PTH) restores bone mass to the osteopenic skeleton, but significant questions remain as to the underlying mechanisms. The receptor for advanced glycation end products (RAGE) is a multiligand receptor of the immunoglobulin superfamily; however, recent studies indicate a role in bone physiology. We investigated the significance of RAGE to hormone-induced increases in bone by treating 10-wk-old female Rage-knockout (KO) and wild-type (WT) mice with human PTH-(1-34) at 30 μg•kg-1•day -1 or vehicle control, 7 days/wk, for 7 wk. PTH produced equivalent relative gains in bone mineral density (BMD) and bone mineral content (BMC) throughout the skeleton in both genotypes. PTH-mediated relative increases in cortical area of the midshaft femur were not compromised in the null mice. However, the hormone-induced gain in femoral cancellous bone was significantly attenuated in Rage-KO mice. The loss of RAGE impaired PTHmediated increases in femoral cancellous bone volume, connectivity density, and trabecular number but did not impact increases in trabecular thickness or decreases in trabecular spacing. Disabling RAGE reduced femoral expression of bone formation genes, but their relative PTH-responsiveness was not impaired. Neutralizing RAGE did not attenuate vertebral cancellous bone response to hormone. Rage-null mice exhibited an attenuated accrual rate of bone mass, with the exception of the spine, and an enhanced accrual rate of fat mass. We conclude that RAGE is necessary for key aspects of the skeleton's response to anabolic PTH. Specifically, RAGE is required for hormone-mediated improvement of femoral trabecular architecture but not intrinsically necessary for increasing cortical thickness.

Original languageEnglish (US)
Pages (from-to)E714-E725
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume298
Issue number3
DOIs
StatePublished - Mar 2010

Keywords

  • Anabolic
  • High-mobility group box 1 protein
  • Osteoblast
  • Osteoimmunology
  • Osteoporosis
  • Receptor for advanced glycation end products

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

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