Introduction: Recent data suggest that lipid metabolism imbalances affect bone cell function and therefore may result in the development of osteoporosis. We investigated the role of apolipoprotein-E (ApoE), a plasma protein playing cardinal role in lipoprotein metabolism, in the regulation of osteoblast and osteoclast function and the pathogenesis of osteoporosis.
Material and methods: We used apoE deficient (ApoE−/−) and C57BL/6 (control) mice fed chow (CD) or western-type diet (WTD) for 24 weeks. Calcein was injected for the determination of new bone formation rate. Following sacrifice, lumbar vertebrae and femora were removed and cortical and cancellous bone quality was evaluated using microCT. TRAP stain was used for osteoclasts detection and von-Kossa for mineralized bone visualization. Dynamic histomorphometry was employed for the assessment of bone formationdegradation rate. Bone marrow mesenchymal stem cells (BMMSC) were isolated from mice femora and then assessed for the expression of the osteoblastic and lipoblastic regulators, Runx2 and PPARγ respectively, using western blotting, flow cytometry and RT-PCR.
Results: i) ApoE−/− WTD did not develop obesity and their BM was devoid of adipocytes, in contrast to the control mice. ii) Osteoclast number was significantly increased, while bone synthesis was significantly reduced in ApoE−/− WTD mice, compared to the other groups. iii) Static and dynamic histomorphometry showed that ApoE−/− WTD developed osteoporosis. iv) BMMSCs from ApoE−/− WTD mice displayed significantly reduced Runx2 expression at both protein and mRNA levels compared to the other groups. v) PPARγ expression was significantly increased in ApoE−/− CD mice in contrast to the ApoE−/− WTD and the other animal groups.
Conclusions: i) ApoE deficiency affects osteoblast and osteoclast function and thus bone remodeling. ii) The absence of ApoE prevents obesity and BM adipocity, but predisposes to the development of osteoporosis following exposure to WTD, in mice.
17 - 20 May 2014
European Calcified Tissue Society