ApoE gene deficiency enhances the reduction of bone formation induced by a high-fat diet through the stimulation of p53-mediated apoptosis in osteoblastic cells

Hideyuki Hirasawa, Shinya Tanaka, Akinori Sakai, Masato Tsutsui, Hiroaki Shimokawa, Hironori Miyata, Sawako Moriwaki, Shumpei Niida, Masako Ito, Toshitaka Nakamura

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

Abstract

Osteoblast apoptosis increased in the tibias of apoE-/- mice fed with a high-fat diet, decreasing bone formation. The expression of p53 mRNA in marrow adherent cells increased. LDL or oxidized LDL increased apoptosis in the calvarial cells of apoE-/- mice. The increase in p53-mediated apoptosis is apparently related to a high-fat diet-induced osteopenia in apoE-/- mice. Introduction: The effects of high-fat loading and the apolipoprotein E (apoE) gene on bones have not been elucidated. We hypothesized that apoE gene deficiency (apoE-/-) modulates the effects of high-fat loading on bones. Materials and Methods: We assessed this hypothesis using wild type (WT) and apoE-/- mice fed a standard (WTS and ApoES groups) or a high-fat diet (WTHf and ApoEHf groups). The concentration of serum lipid levels and bone chemical markers were measured. Histomorphometry of the femurs was performed using μCT and a microscope. Bone marrow adherent cells from the femurs were used for colony-forming unit (CFU)-fibroblastic (CFU-f) assay and mRNA expressions analysis. The apoptotic cells in the tibias were counted. TUNEL fluorescein assay and Western analysis were performed in cultures of calvarial cells by the addition of low-density lipoprotein (LDL) or oxidized LDL. Results: In the ApoEHf group, the values of cortical bone volume and trabecular and endocortical bone formation of the femurs decreased, and urinary deoxypyridinoline increased. Subsequent analysis revealed that the number of apoptotic cells in the tibias of the ApoES group increased, and more so in the ApoEHf group. The ratio of alkaline phosphatase-positive CFU-f to total CFU-f was decreased in the ApoEHf group. p53 mRNA expression in adherent cells of the apoE-/- mice increased and had a significantly strong positive correlation with serum LDL. TUNEL fluorescein assay of osteoblastic cells revealed an increase of apoptotic cells in the apoE-/- mice. The number of apoptotic cells in the apoE-/- mice increased with the addition of 100 μg/ml LDL or oxidized LDL. The p53 protein expression in apoE-/- cells exposed to 100 μg/ml LDL or oxidized LDL increased. Conclusions: We concluded that apoE gene deficiency enhances the reduction of bone formation induced by a high-fat diet through the stimulation of p53-mediated apoptosis in osteoblastic cells.

Original languageEnglish
Pages (from-to)1020-1030
Number of pages11
JournalJournal of Bone and Mineral Research
Volume22
Issue number7
DOIs
Publication statusPublished - 2007 Jul

Keywords

  • Apolipoprotein E
  • Apoptosis
  • Lipid peroxide
  • Low-density lipoprotein
  • Osteopenia

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Fingerprint Dive into the research topics of 'ApoE gene deficiency enhances the reduction of bone formation induced by a high-fat diet through the stimulation of p53-mediated apoptosis in osteoblastic cells'. Together they form a unique fingerprint.

Cite this