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 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. PTH1-34 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 PTH1-34. 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.
Schlaeppi
J M
JM
Novartis Pharma Research, Basel, Switzerland.
Gutzwiller
S
S
Finkenzeller
G
G
Fournier
B
B
D001943:Breast Neoplasms; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008222:Lymphokines / Q000235:genetics*; D010006:Osteoblasts / Q000378:metabolism*; D011994:Recombinant Proteins; D019379:Teriparatide / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D005938:Glucocorticoids; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019379:Teriparatide; D003907:Dexamethasone; D002117:Calcitriol