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Influence of Estradiol on Vascular Endothelial Growth Factor Expression in Bone: A Study in Göttingen Miniature Pigs and Human Osteoblasts
- Source :
- Calcified Tissue International. 80:184-191
- Publication Year :
- 2007
- Publisher :
- Springer Science and Business Media LLC, 2007.
-
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.
- Subjects :
- Vascular Endothelial Growth Factor A
medicine.medical_specialty
Bone density
Miniature pig
Swine
Angiogenesis
Keratan sulfate
Ovariectomy
Endocrinology, Diabetes and Metabolism
Blotting, Western
Osteoclasts
Bone and Bones
Bone remodeling
chemistry.chemical_compound
Endocrinology
Internal medicine
medicine
Animals
Humans
Orthopedics and Sports Medicine
Osteoblasts
Estradiol
biology
Chemistry
Ossification
Cartilage
biology.organism_classification
Vascular endothelial growth factor
Receptors, Vascular Endothelial Growth Factor
medicine.anatomical_structure
Swine, Miniature
Female
medicine.symptom
Subjects
Details
- ISSN :
- 14320827 and 0171967X
- Volume :
- 80
- Database :
- OpenAIRE
- Journal :
- Calcified Tissue International
- Accession number :
- edsair.doi.dedup.....bb6ae0f086920b9f81ba678131b87e9a