Artikel
VEGF-expression in osteonecrosis of the femoral head
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Veröffentlicht: | 16. Oktober 2008 |
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Gliederung
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Objective: VEGF has recently been shown to play an important role during bone remodeling. The role of VEGF in steroid related femoral head necrosis has not been investigated so far. This study was conducted to reveal VEGF expression in osteoblasts after glucocorticoid (GC) treatment in vitro and in vivo, and to explore VEGF expression during late stage femoral head necrosis.
Methods: Necrotic femoral heads were obtained during hip alloplasty surgery. AZAN, GOLDNER and VAN GIESON staining were performed to reveal the bone structure of the proximal femur. VEGF-protein and VEGF receptor-2 (VEGFR-2) were localized by immunohistochemistry in tissue sections of necrotic femoral heads. Expression of VEGF-, VEGFR-2- and VEGF splice variants-mRNA in cultured primary osteoblasts were analyzed by RTPCR. Regulation of VEGF protein was quantified in supernatants of cultivated osteoblasts by ELISA after exposure to glucucocorticoids and in bone samples of necrotic femoral heads.
Results: Osteoblasts of necrotic bone areas of femoral heads revealed increased immunoreactivity to VEGF compared to those from non-necrotic areas. ELISA confirmed VEGF upregulation in necrotic bone areas in samples of necrotic femoral heads of ARCO stage IV. The splice variants with the strongest angiogenic potency (VEGF121 and VEGF165) were detectable in cultured osteoblasts. VEGF production was clearly downregulated in supernatants of cultivated osteoblasts after 24 hours of co-incubation with glucucocorticoids, thus suggesting a direct influence of GC-induced VEGF decrease in the pathomechanism of early stage femoral head necrosis (ARCO stage I-II)
Conclusion: VEGF is produced in osteoblasts, and its concentration is strongly decreased after exposure to GC in vitro. In contrast, VEGF expression increases in osteoblasts of necrotic femoral heads with late stage disease. The observed increase of VEGF in later stage femoral head necrosis might stimulate the ingrowth of reparative arterioles into the necrotic femoral head.