| Abstract: | Angiogenesis is essential to both normal and pathological bonephysiology. Vascular endothelial growth factor (VEGF) has been implicated in angiogenesis, whereas transforming growth factor- 1 (TGF-1) modulates bone differentiation, matrixformation, and cytokine expression. The purpose of this study was toinvestigate the relationship between TGF-1 and VEGF expression inosteoblasts and osteoblast-like cells. Northern blot analysis revealedan early peak of VEGF mRNA (6-fold at 3 h) in fetal rat calvarial cellsand MC3T3-E1 osteoblast-like cells after stimulation with TGF-1 (2.5 ng/ml). The stability of VEGF mRNA in MC3T3-E1 cells was not increasedafter TGF-1 treatment. Actinomycin D inhibited the TGF-1-inducedpeak in VEGF mRNA, whereas cycloheximide did not. Blockade of TGF-1signal transduction via a dominant-negative receptor II adenovirussignificantly decreased TGF-1 induction of VEGF mRNA. Additionally,TGF-1 induced a dose-dependent increase in VEGF protein expressionby MC3T3-E1 cells (P < 0.01).Dexamethasone similarly inhibited VEGF protein expression. BothTGF-1 mRNA and VEGF mRNA were concurrently present in rat membranousbone, and both followed similar patterns of expression during ratmandibular fracture healing (mRNA and protein). In summary,TGF-1-induced VEGF expression by osteoblasts and osteoblast-likecells is a dose-dependent event that may be intimately related to bonedevelopment and fracture healing. |
