title: Transforming growth factor-beta1 modulates the expression of vascular endothelial growth factor by osteoblasts.
abstract: Angiogenesis is essential to both normal and pathological bone physiology. Vascular endothelial growth factor (VEGF) has been implicated in angiogenesis, whereas transforming growth factor-beta1 (TGF-beta1) modulates bone differentiation, matrix formation, and cytokine expression. The purpose of this study was to investigate the relationship between TGF-beta1 and VEGF expression in osteoblasts and osteoblast-like cells. Northern blot analysis revealed an early peak of VEGF mRNA (6-fold at 3 h) in fetal rat calvarial cells and MC3T3-E1 osteoblast-like cells after stimulation with TGF-beta1 (2.5 ng/ml). The stability of VEGF mRNA in MC3T3-E1 cells was not increased after TGF-beta1 treatment. Actinomycin D inhibited the TGF-beta1-induced peak in VEGF mRNA, whereas cycloheximide did not. Blockade of TGF-beta1 signal transduction via a dominant-negative receptor II adenovirus significantly decreased TGF-beta1 induction of VEGF mRNA. Additionally, TGF-beta1 induced a dose-dependent increase in VEGF protein expression by MC3T3-E1 cells (P < 0.01). Dexamethasone similarly inhibited VEGF protein expression. Both TGF-beta1 mRNA and VEGF mRNA were concurrently present in rat membranous bone, and both followed similar patterns of expression during rat mandibular fracture healing (mRNA and protein). In summary, TGF-beta1-induced VEGF expression by osteoblasts and osteoblast-like cells is a dose-dependent event that may be intimately related to bone development and fracture healing.
authors.affiliation: Department of Surgery, University of Connecticut, Farmington, Connecticut 06032, USA.
authors.forename: P B
authors.initials: PB
authors.lastname: Saadeh
authors.forename: B J
authors.initials: BJ
authors.lastname: Mehrara
authors.forename: D S
authors.initials: DS
authors.lastname: Steinbrech
authors.forename: M E
authors.initials: ME
authors.lastname: Dudziak
authors.forename: J A
authors.initials: JA
authors.lastname: Greenwald
authors.forename: J S
authors.initials: JS
authors.lastname: Luchs
authors.forename: J A
authors.initials: JA
authors.lastname: Spector
authors.forename: H
authors.initials: H
authors.lastname: Ueno
authors.forename: G K
authors.initials: GK
authors.lastname: Gittes
authors.forename: M T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D000818:Animals; D002146:Bony Callus / Q000378:metabolism; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D005333:Fetus / Q000166:cytology; D050723:Fractures, Bone / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014945:Wound Healing / Q000502:physiology
chemical_list: D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D005938:Glucocorticoids; D008222:Lymphokines; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003907:Dexamethasone