Vascular endothelial growth factors signalling in normal human dental pulp: a study of gene and protein expression

Abstract

In the well-vascularized dental pulp vascular endothelial growth factor A (VEGF-A) is expressed. Vascular endothelial growth factor A is a member of the VEGF family, which includes VEGFs-B, -C, and -D. The latter three have not been investigated in the pulp. Vascular endothelial growth factors C and D are the only ligands for vascular endothelial growth factor receptor (VEGFR)-3, which is usually expressed in lymphatic endothelium. They can also activate VEGFR-2, the main angiogenic receptor. We aimed to study VEGFs signalling in human dental pulp at the gene level and to identify the cellular source for protein expression using immunolabelling. All VEGFs (-A, -B, -C, and -D) were expressed in the pulp and may exert both autocrine and paracrine effects in blood vessels and immune cells found to be equipped with VEGFRs-2 and -3. Lymphatic vessel endothelial hyaluronan receptor-positive macrophages, known to be involved in angiogenesis, were found in the pulp, whereas lymphatic vessels were not detected. Twenty-six of 84 VEGF signalling genes, including VEGFR-3, were expressed at a significantly higher level in the pulp than in the control periodontal ligament. In conclusion, the normal human pulp represents a tissue with relatively high VEGF signalling involving both immune responses and vascular activity.

Gene expression of growth factors with angiogenic potential in human dental pulp tissue from teeth with complete and incomplete root development

“…The findings of the present study and its clinical significance can be summarized as follows: There was expression of all the genes studied (ANG2, VEGFA, NRP1, VEGFR1, VEGFR2, TGFb1 and TGFbR1) in teeth with complete and incomplete root development indicating that the dental pulp has an enormous angiogenic potential over its lifetime (G€ uven et al 2007, Matuella et al 2007, Virtej et al 2013). Moreover, when comparing both groups, because the VEGFA expression in teeth with complete root development was greater, it could be inferred that there is significantly more potential for initiating angiogenic activity in these teeth than in teeth with incomplete root development where mastication could be a determining factor.…”

“…These processes are mediated by growth factors such as vascular endothelial growth factor (VEGFA), basic fibroblastic growth factor (bFGF), transforming growth factor beta (TGFß), angiogenin, angiopoietin 2 (ANG-2), epidermal growth factor (EGF), heparin-binding epidermal growth factor (HB-EGF) and platelet-derived growth factor (PDGF) amongst others (Derringer & Linden 2007, Mattuella et al 2007, El Karim et al 2009, Virtej et al 2013, Caviedes-Bucheli et al 2017. These processes are mediated by growth factors such as vascular endothelial growth factor (VEGFA), basic fibroblastic growth factor (bFGF), transforming growth factor beta (TGFß), angiogenin, angiopoietin 2 (ANG-2), epidermal growth factor (EGF), heparin-binding epidermal growth factor (HB-EGF) and platelet-derived growth factor (PDGF) amongst others (Derringer & Linden 2007, Mattuella et al 2007, El Karim et al 2009, Virtej et al 2013, Caviedes-Bucheli et al 2017.…”

Glial Network Responses to Polymicrobial Invasion of Dentin

“…Telacytes were characterized as astrocyte-like glia by low-level expression of GFAP where the product was not detected immunohistochemically but showed high expression of S100B mRNA in accord with immunologically detected expression of this protein [Farahani et al, 2011]. These cells also expressed genes encoding vascular endothelial growth factor (VEGF) [Virtej et al, 2013], nerve growth factor (NGF) and low-affinity nerve growth factor receptor (P 75 NTR) [Woodnutt et al, 2000]. Telacytes also expressed genes coding for enzymes involved in metabolic recycling of glutamate, namely glutamine synthetase (GLUL) [Bucher et al, 2013] and the glutamate transporter (GLT-1) [Lundgaard et al, 2013].…”

Role of Angiogenesis in Endodontics: Contributions of Stem Cells and Proangiogenic and Antiangiogenic Factors to Dental Pulp Regeneration

“…The treatment of dental pulp tissue with 0–50 ng/mL recombinant human VEGF or recombinant human FGF-2 for 7 days resulted in increased number of microvessels and neovascularization (62). VEGF-A is a member of VEGF family that is more extensively studied (63). Other VEGF family members include VEGF-B, -C, and -D, which are also expressed in the dental pulp tissue and have autocrine and paracrine effects during angiogenesis (63).…”

“…VEGF-A is a member of VEGF family that is more extensively studied (63). Other VEGF family members include VEGF-B, -C, and -D, which are also expressed in the dental pulp tissue and have autocrine and paracrine effects during angiogenesis (63). …”