Mechanism of transforming growth factor-β1-induced expression of vascular endothelial growth factor in murine osteoblastic MC3T3-E1 cells

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Abstract

Transforming growth factor-β1 (TGF-β1), an abundant growth factor in bone matrix, has been shown to be involved in bone formation and fracture healing. The mechanism of action of the osteogenic effect of TGF-β1 is not clearly understood. In this study, we found that the addition of TGF-β1 to murine osteoblastic MC3T3-E1 cells induced vascular endothelial growth factor (VEGF) mRNA production. VEGF mRNA levels reached a plateau within 2 h after the addition of TGF-β1. The induction was superinduced by cycloheximide and blocked by actinomycin D. Ro 31-8220, a protein kinase C inhibitor, abrogated the induction. In addition, curcumin, an inhibitor for transcription factor AP-1, also blocked the induction. Electrophoretic mobility shift assay revealed an enhanced binding of transcription factors AP-1 and NF-κB. Transient transfection experiment showed that VEGF promoter activity increased 3.6-fold upon TGF-β1 stimulation. Immunoblot analysis showed that the amount of secreted VEGF was elevated in the medium 4 h after TGF-β1 stimulation. Our results therefore suggest that at least part of the osteogenic activity of TGF-β1 may be attributed to the production of VEGF. Copyright (C) 2000 Elsevier Science B.V.

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Chua, C. C., Hamdy, R. C., & Chua, B. H. L. (2000). Mechanism of transforming growth factor-β1-induced expression of vascular endothelial growth factor in murine osteoblastic MC3T3-E1 cells. Biochimica et Biophysica Acta - Molecular Cell Research, 1497(1), 69–76. https://doi.org/10.1016/S0167-4889(00)00040-9

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