Bone Abstracts (2013) 1 PP353 | DOI: 10.1530/boneabs.1.PP353

Apolipoprotein-E deficiency prevents obesity but predisposes to the development of osteoporosis following long-term exposure to Western-type diet, in mice

Nicholaos Papachristou1, Elena Kalyvioti1, Irene-Eva Triantaphyllidou1, Eleni Karavia2, Eva Plakoula1, Harry Blair3, Kyriakos Kypreos2 & Dionysios Papachristou1,3


1Unit of Bone and Soft Tissue Studies, Department of Histology, School of Medicine, University of Patras, Rion-Patras, Greece; 2Department of Pharmacology, School of Medicine, University of Patras, Rion-Patras, Greece; 3Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.


Introduction: Recent data suggest that imbalances in lipid metabolism affect bone cell function resulting in osteoporosis. Here, we investigated the role of apolipoprotein E (ApoE), essential component of chylomicron and very low density Lipoprotein metabolic pathways, in the regulation of osteoblast and osteoclast function and thus in the pathogenesis of osteoporosis.

Material and methods: We used apoE deficient (ApoE−/−) and wild type (C57BL/6) mice (ten animals/ group). Mice were fed chow or standard western-type diet (WTD) for 24 weeks. Body weight measurements were obtained every 6 weeks. Two and seven days before euthanasia calcein was injected intraperitonealy for the determination of new bone formation rate. Following sacrifice, lumbar vertebrae and femora were removed and quantitative/qualitative study of the cortical and cancellous bone was performed using microCT scanner. TRAP stain was used for osteoclasts detection and von-Kossa for mineralized bone visualization. Static and dynamic histomorphometry were employed for the determination of bone formation-degradation rate.

Results: i) ApoE−/− mice fed WTD did not develop obesity, in contrast to the C57BL/6 (control) mice. ii) Osteoclast number was significantly increased, while bone synthesis was significantly reduced in ApoE−/− mice fed WTD, in contrast to the other groups. iii) Static and dynamic histomorphometry showed that ApoE−/− mice fed WTD developed osteoporosis.

Conclusions: i) ApoE plays a central role in the regulation of osteoblast and osteoclast function and thus in bone remodeling. ii) The absence of ApoE prevents obesity, but predisposes to the development of osteoporosis after the consumption of high-fat diet.

Acknowledgments: This study is supported by ‘The European Community’s Seventh Framework Programme (FP7-IR-Grant-PIRG06-GA-256402)’ and The University of Patras ‘Karatheodori’ Research Grant (#D155) (All awarded to DJ Papachristou) and is part of the research network ‘OsteoNet’ of the University of Patras activities.