gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2016)

25.10. - 28.10.2016, Berlin

ApoE deficiency in osteoblasts leads to a low bone mass phenotype in mice

Meeting Abstract

  • presenting/speaker Tobias Schmidt - Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Orthopädie, Hamburg, Germany
  • Brigitte Müller - Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Orthopädie, Hamburg, Germany
  • Alexander Bartelt - Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Orthopädie, Hamburg, Germany
  • Till Köhne - Universitätsklinikum Hamburg-Eppendorf, Poliklinik für Kieferorthopädie, Hamburg, Germany
  • Frank T. Beil - Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Orthopädie, Hamburg, Germany
  • Wolfgang Rüther - Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Orthopädie, Hamburg, Germany
  • Thorsten Schinke - Universitätsklinikum Hamburg-Eppendorf, Institut für Osteologie und Biomechanik, Hamburg, Germany
  • Andreas Niemeier - Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Orthopädie, Hamburg, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2016). Berlin, 25.-28.10.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocPO30-1323

doi: 10.3205/16dkou794, urn:nbn:de:0183-16dkou7949

Veröffentlicht: 10. Oktober 2016

© 2016 Schmidt et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objectives: Apolipoprotein E (ApoE) is an important component of lipoproteins. As a ligand for members of the LDL receptor family, it mediates the endocytosis of these lipoproteins. ApoE deficiency in mice causes an accumulation of remnant lipoproteins but also results in a high-bone mass phenotype with increased bone formation while bone resorption is unaffected. Up to now it is unknown from which cell type the ApoE that regulates bone remodeling is derived from. The objective of this study was to explore the role of osteoblast-ApoE in the regulation of bone mass in vivo.

Methods: In order to specifically analyze the function of osteoblast-ApoE in vivo we generated a conditional ApoE knockout-mouse (Cre-loxP). Runx2-Cre mice were crossed to ApoEflox/flox mice to generate mice lacking ApoE in the osteoblast lineage. Histomorphometry and µCT was performed on trabecular vertebral and femoral bone of three and six months old females. Bone turnover makers alkaline phosphatase, osteocalcin and DPD/creatinine were measured in the serum and urine by ELISA.

Results and Conclusion: Interestingly, the specific deletion of ApoE in the osteoblast lineage results in an age-dependent bone phenotype which does not reflect the global ApoE knock-out phenotype. Hence, three months old ApoEflox/flox Runx2-Cre+ female mice do not display an altered bone mass phenotype yet, whereas the trabecular bone mass of six months old ApoEflox/flox Runx2-Cre+ females is significantly reduced compared to ApoEflox/flox littermates. This reduction is caused by an increased number of osteoclasts and increased bone resorption, while the bone formation rate remains unchanged. In addition, these mice exhibit an elevated osteocalcin concentration in the serum.

These findings confirm that ApoE has a powerful regulatory function in bone remodeling. The effects of osteoblast ApoE and systemic (mostly liver-derived) ApoE on the regulation of trabecular bone mass appear to be diverging. The lack of ApoE in osteoblasts triggers a yet to be identified signal that stimulates osteoclastic bone resorption. It is conceivable that ApoE, via its effect on osteocalcin production by osteoblasts, plays a relay function in the postprandial energy metabolism.