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

Abstract

Aim To quantify the expression of angiogenic growth factors (ANG2, VEGFA, TGFß1) and their corresponding receptors (VEGFR1, VGFR2, NRP1 and TGFßR1) in human dental pulps from extracted third molars with complete and incomplete root development. Methodology Fifty‐six dental pulp samples obtained from freshly extracted human third molars were divided equally into two groups according to their stage of root development; 28 third molars with complete root development and 28 third molars with incomplete root development. All samples were processed and total RNA was extracted, cDNA was then synthetized for each sample and the target genes expression profiles for ANG2, VEGFA, VEGFR1, VEGFR2, NRP1, TGFß1 and TGFßR1 were obtained by RT2‐PCR. The data was analysed with a Student's t‐test to compare the replicate ∆∆Ct values for each gene. Results Teeth with incomplete root development were associated with a significantly greater gene expression of TGFβR1 (P = 0.03), whereas in teeth with complete root development the genes that had significantly greater expression were VEGFA (P = 0.04). Conclusion The angiogenic growth factors (ANG2, VEGFA, TGFβ1) and their receptors (NRP1, VEGFR1, VEGFR2 and TGFßR1) were expressed in pulps of teeth with complete and incomplete root development measured by RT2‐PCR, with TGFBR1 genes being significantly different in teeth with incomplete root development and VEGFA genes in teeth with complete root development.

Expression of early angiogenesis indicators in mature versus immature teeth

“…VEGFA is the main pro-angiogenic growth factor which is responsible for survival, proliferation, migration and sprouting of the capillary vessel [1]. Endothelial cells activated by HIF-1 express growth factors receptors such as VEGFR2 and NRP1 in their membrane in order to allow VEGFA to bind them and start the angiogenic process [1,13].…”

“…During normoxia, ANG1 binds to its receptor TIE2, forming an ANG1/TIE2 complex, which induces an association between pericytes and endothelial cells, producing vasculature stabilization which acts as an inhibitor of angiogenesis. In contrast, during hypoxia ANG2 binds to TIE2, and the ANG2/TIE2 complex inhibits TIE2 phosphorylation even in the presence of ANG1 [1,16,17]. ANG2/TIE2 leads to blood vessel destabilization and in the presence of VEGF promotes migration and proliferation of endothelial cells initiating angiogenesis [15,17].…”

“…Dental pulp of immature apex teeth could have an increased cellular activity related to dentine formation which progressively narrows the root canal until complete apex formation. In these teeth, the existing blood vessels in dental pulp are capable of maintaining normoxia with low ranges of angiogenesis [1]. While in teeth with mature apexes, stimuli such as mastication, bruxism and ageing could induce a cellular activity to increase dentine formation.…”

“…While in teeth with mature apexes, stimuli such as mastication, bruxism and ageing could induce a cellular activity to increase dentine formation. This higher activity promotes the expression of angiogenic growth factors due to imbalance between oxygen supply and its consumption, in order to form new blood vessels [1,18].…”

“…Adequate oxygen concentration is necessary for dental pulp homeostasis [1]. Dental pulp cells require a specific oxygen concentration for ATP production by REDOXs reactions for protein synthesis, which is necessary for its metabolic functions that vary over tooth's life [2,3].…”