Angiogenesis in the apical papilla of immature permanent teeth

Abstract

Dental trauma, caries or developmental anomalies may result in reversible or irreversible injury to the dental pulp in immature permanent teeth and this presents a clinical conundrum. Immature teeth possess a more favourable healing potential, and this is partly contingent on the vascularity, and angiogenic potential of the resident cells and growth factors. Moreover, the apical papilla is a tissue unique to these teeth and plays an important role in root development and healing. Angiogenesis is a fundamental process in development and disease and is incumbent upon an intricate interplay of angiogenic genes, growth factors and their cognate receptors. The dental pulp is not a “doomed organ” (Rebel 1922) and is capable of healing. Hence, current therapies are aimed at preservation of pulp vitality and facilitating apexogenesis, but treatment outcomes are not always predictable. An increased understanding of angiogenic signalling in the apical region at a molecular level may improve this. This research explored the angiogenic potential of the apical papilla in healthy immature permanent human teeth and serves as a baseline for understanding potential responses to disease. As well as examining protein expression in the apical papilla tissue, the distribution and relative mRNA levels of angiogenic growth factors (VEGF, Ang-1, Ang-2), receptor proteins (VEGFR2 and Tie-2), and cell-surface markers (CD34 and CD45) were investigated.

Immunohistochemistry and gene expression experiments conducted on the apical papilla showed that this tissue was comprised of angiogenic growth factors and receptors and few resident cells and blood vessels, demonstrating evidence that it is capable of partaking in and promoting angiogenic signalling. Endothelial cells were the predominant cells expressing these markers but expression on other cell types including fibroblasts and immature mesenchymal cells suggests they play contributory roles. VEGF, Ang-1, and Tie-2 exhibited greater immunopositivity and higher cell counts than Ang2 in the apical papilla, while CD34 and CD45 were sparsely distributed. Real-time polymerase chain reaction corroborated these results and revealed differences in gene expression between the apical and coronal regions. The differential expression of VEGF and angiopoietins and their receptor mRNA and protein in the apical papilla suggests the potential for these growth factors to contribute to physiological root development and pulp healing following injury. This study has enhanced our understanding of angiogenesis in healthy dental pulps, and contributes to the body of knowledge related to potential use of angiogenic-modulatory factors in vital pulp therapies.