Calcified Tissue International

, Volume 80, Issue 3, pp 184–191

Influence of Estradiol on Vascular Endothelial Growth Factor Expression in Bone: A Study in Göttingen Miniature Pigs and Human Osteoblasts

  • T. Pufe
  • H. Claassen
  • K. E. Scholz-Ahrens
  • D. Varoga
  • W. Drescher
  • A. T. M. Franke
  • C. Wruck
  • W. Petersen
  • C. Cellarius
  • J. Schrezenmeir
  • C.-C. Glüer
Article

Abstract

Ovariectomy (OVX) in animal models is an accepted method to simulate postmenopausal osteoprosis. Vascular endothelial growth factor (VEGF) has been recently shown to play an important role during endochondral bone formation, hypertrophic cartilage remodeling, ossification, and angiogenesis. We hypothesized that reduced VEGF expression in bone contributes to OVX-induced bone loss and tested it in a miniature pig model and in vitro using human osteoblasts. Seventeen primiparous sows (Göttingen miniature pigs) were allocated to two experimental groups when they were 30 months old: a control group (n = 9) and an OVX group (n = 8). After 15 months, VEGF levels in lumbar vertebrae were measured by enzyme-linked immunosorbent assay and verified by Western blot analysis. VEGF and its receptor (VEGFR) were localized by immunohistochemistry. Expression of VEGF mRNA was analyzed by real-time reverse-transcription polymerase chain reaction. Differently sulfated glycosaminoglycans were localized in subchondral bone histochemically. Osteoblasts were immunopositive for VEGF. VEGF concentration in the vertebra was 27% lower in OVX miniature pigs. VEGFR-2 could be immunostained on osteoblasts. VEGF mRNA and protein were detectable in the lumbar vertebrae of all animals. In subchondral trabecular bone of OVX animals, significantly more islands of mineralized cartilage containing chondroitin 4- and 6-sulfate or keratan sulfate occurred compared to the control group. The occurrence of remnants of mineralized cartilage in subchondral bone of the OVX group may be caused by a delayed bone turnover due to low VEGF levels. In vitro experiments revealed an increase of VEGF in the supernatant of osteoblasts after incubation with estradiol. In conclusion, estrogen seems to be a key factor for regulation of VEGF expression in bone. Loss of VEGF due to menopause may be a reason for reduction of bone density.

Keywords

Vascular endothelial growth factor Estradiol Göttingen miniature pig Trabecular bone Ovariectomy Glycosaminoglycan 

Copyright information

© Springer Science+Business Media, Inc. 2007

Authors and Affiliations

  • T. Pufe
    • 1
  • H. Claassen
    • 1
    • 2
  • K. E. Scholz-Ahrens
    • 3
  • D. Varoga
    • 1
  • W. Drescher
    • 4
  • A. T. M. Franke
    • 1
  • C. Wruck
    • 1
  • W. Petersen
    • 5
  • C. Cellarius
    • 1
  • J. Schrezenmeir
    • 3
  • C.-C. Glüer
    • 6
  1. 1.Department of AnatomyChristian-Albrechts-University KielKielGermany
  2. 2.Department of Anatomy and Cell BiologyMartin-Luther-University Halle-WittenbergHalle (Saale)Germany
  3. 3.Institute of Physiology and Biochemistry of NutritionFederal Research Centre for Nutrition and FoodKielGermany
  4. 4.Department of OrthopedicsUniversity Hospital FrankfurtFrankfurtGermany
  5. 5.Department of Trauma SurgeryUniversity Hospital MunsterMünsterGermany
  6. 6.Division of Medical Physics, Department of Diagnostic RadiologyUniversity Hospital Schleswig-HosteinKielGermany

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