1,25-DIHYDROXYVITAMIN D3 Induces the expression of vascular endothelial growth factor in osteoblastic cells

Angiogenesis is a fundamental process in skeletal development and repair, and previous studies indicate that vascular endothelial growth factor (VEGF), an endothelial cell-specific angiogenic factor, may be involved in bone formation and repair Therefore, we studied the hormonal regulation of VEGF e...

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Published in:Endocrine research 1997, Vol.23 (3), p.213-229
Main Authors: Schlaeppi, Jean-Marc, Gutzwiller, Sabine, Finkenzeller, Günter, Fournier, Brigitte
Format: Article
Language:English
Subjects:
Breast Neoplasms
Calcitriol - pharmacology
Cell Line
Dexamethasone - pharmacology
Endothelial Growth Factors - genetics
Gene Expression - drug effects
Glucocorticoids - pharmacology
Humans
Lymphokines - genetics
Osteoblasts - metabolism
Recombinant Proteins
Teriparatide - pharmacology
Transfection
Tumor Cells, Cultured
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
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Summary:Angiogenesis is a fundamental process in skeletal development and repair, and previous studies indicate that vascular endothelial growth factor (VEGF), an endothelial cell-specific angiogenic factor, may be involved in bone formation and repair Therefore, we studied the hormonal regulation of VEGF expression in SaOS-2 osteoblast-like cells, both at the protein level, and at the transcriptional level by transient transfection experiments. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3], increased VEGF expression by approximately 3-fold, and the increase was dose dependent, with maximum stimulation between 1.0 and 10 nM of 1,25-(OH)2D3. Up-regulation of VEGF protein was detected already after 6 h of treatment. VEGF up-regulation was also observed in ROS-17/2.8 and OHS-4 osteoblast-like cells but not in MCF-7 and MDA-MB231 breast carcinoma cells. Dexamethasone (Dex) decreased VEGF expression to 40% of the control, but when added together with 1,25-(OH)2D3, had no effects on the up-regulation of VEGF by 1,25-(OH)2D3. PTHi-34 stimulated weakly VEGF expression, but combined with 1,25-(OH)2D3, resulted in a close to 5-fold stimulation. A 4-day pretreatment of the cells with Dex increased the vitamin D3 receptor expression and resulted in a stronger stimulation of VEGF by 1,25-(OH)2D3, alone or in combination with PTHi-34. The results show that the VEGF promoter is a target of 1,25-(OH)2D3 regulation in osteoblasts, despite the lack of classical vitamin D3 responsive elements. The up-regulation of VEGF in osteoblast-like cells by calciotropic hormones provides additional evidence of the involvement of VEGF in bone metabolism.
ISSN:0743-5800
1532-4206
DOI:10.3109/07435809709031855