Artikel
VEGF (Vascular Endothelial Growth Factor) in osteoporosis in-vivo and in-vitro
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Veröffentlicht: | 28. September 2006 |
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Gliederung
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Objective: Osteoporosis is a disease characterized by low bone mass and an increased susceptibility to fractures. The molecular mechanism of GC induced osteoporosis and the occurrence and function of related cytokines are largely unclear. Aim of this investigation was to analyse the influence of glucocorticoid (GC) treatment on the VEGF expression in-vitro and in an animal model (Göttinger Minipig).
Methods: As part of a larger study, 17 primiparous sows were allocated to 2 experimental groups (control and GC treated animals). Human osteoblasts were used for in vitro assays. VEGF and VEGF receptors were located by immuno-histochemistry. VEGF content in lumbar vertebra and culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA); VEGF mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Spinal bone mineral density (BMD) was assessed in vivo by Quantitative Computed Tomography (QCT).
Results: Strong VEGF concentrations were measured in normal lumbar vertebrae whereas VEGF concentrations were 60 % lower (p<0.0001) in GC-treated minipigs. Our in-vitro experiments with cultured osteoblasts confirmed the in-vivo findings. Osteoblasts were immunopositive for VEGF. VEGF receptors VEGFR-2 (KDR, flk-1) and VEGFR-1 (flt-1) could be immunostained on osteoclasts and osteoblasts. VEGF mRNA and protein was detectable in all lumbar vertebrae. Incubation with dexamethasone decreased VEGF secretion also in vitro to 39 % (p<0.01). BMD assessed by QCT at study start was comparable for the control group and the GC treated group. Over the 15 month duration of the study BMD was stable in the control group (n=9) (-0.46±2.2%, n.s.) but decreased in the GC group (n=8) by –12.8±5.5%. The difference in the rate of loss was highly significant (p<0.0014). VEGF levels were significantly correlated with this change in BMD (r=0.7).
Conclusion: VEGF is produced in osteoblasts and its concentration is decreased in GC treated animals as well as in osteoblasts exposed to GC. Since reductions in VEGF concentrations correlate with parallel measurement of bone mineral density in GC treated minipigs and VEGF is as angiogenesis factor suitable for recruiting basic multicellular units (BMU) we hypothesize that VEGF may be an important modulating factor for bone remodeling, specifically in GC induced osteoporosis.