These authors contributed equally to this manuscript.
Increased Bone Formation in Mice Lacking Apolipoprotein E†
Article first published online: 1 NOV 2004
Copyright © 2005 ASBMR
Journal of Bone and Mineral Research
Volume 20, Issue 2, pages 274–282, February 2005
How to Cite
Schilling, A. F., Schinke, T., Münch, C., Gebauer, M., Niemeier, A., Priemel, M., Streichert, T., Rueger, J. M. and Amling, M. (2005), Increased Bone Formation in Mice Lacking Apolipoprotein E. J Bone Miner Res, 20: 274–282. doi: 10.1359/JBMR.041101
The authors have no conflict of interest.
- Issue published online: 4 DEC 2009
- Article first published online: 1 NOV 2004
- Manuscript Accepted: 27 AUG 2004
- Manuscript Revised: 23 JUL 2004
- Manuscript Received: 13 MAR 2004
- apolipoprotein E;
- bone formation;
- vitamin K;
ApoE is a plasma protein that plays a major role in lipoprotein metabolism. Here we describe that ApoE expression is strongly induced on mineralization of primary osteoblast cultures. ApoE-deficient mice display an increased bone formation rate compared with wildtype controls, thereby showing that ApoE has a physiologic function in bone remodeling.
Introduction: Apolipoprotein E (ApoE) is a protein component of lipoproteins and facilitates their clearance from the circulation. This is confirmed by the phenotype of ApoE-deficient mice that have high plasma cholesterol levels and spontaneously develop atherosclerotic lesions. The bone phenotype of these mice has not been analyzed to date, although an association between certain ApoE alleles and BMD has been reported.
Materials and Methods: Primary osteoblasts were isolated from newborn mouse calvariae and mineralized ex vivo. A genome-wide expression analysis was performed during the course of differentiation using the Affymetrix gene chip system. Bones from ApoE-deficient mice and wildtype controls were analyzed using radiography, μCT imaging, and undecalcified histology. Cellular activities were assessed using dynamic histomorphometry and by measuring urinary collagen degradation products. Lipoprotein uptake assays were performed with125I-labeled triglyceride-rich lipoprotein-remnants (TRL-R) using primary osteoblasts from wildtype and ApoE-deficient mice. Serum concentrations of osteocalcin were determined by radioimmunoassay after hydroxyapatite chromatography.
Results:ApoE expression is strongly induced on mineralization of primary osteoblast cultures ex vivo. Mice lacking ApoE display a high bone mass phenotype that is caused by an increased bone formation rate, whereas bone resorption is not affected. This phenotype may be explained by a decreased uptake of triglyceride-rich lipoproteins by osteoblasts, resulting in elevated levels of undercarboxylated osteocalcin in the serum of ApoE-deficient mice.
Conclusion: The specific induction of ApoE gene expression during osteoblast differentiation along with the increased bone formation rate observed in ApoE-deficient mice shows that ApoE has a physiologic role as a regulator of osteoblast function.