The pulpal response to orthodontic force is thought to involve cell damage, inflammation, and wound healing. These situations are likely to be associated with the release of angiogenic growth factors. We therefore investigated human dental pulps to determine if angiogenic changes could be detected after orthodontic force application. Fifteen premolar teeth were treated with straight-wire fixed orthodontic appliances for two weeks, and comparisons were made with 15 untreated control premolar teeth from the same subjects. The teeth were extracted and sectioned. The pulps were removed, divided into 1-mm sections, embedded in collagen, and cultured in growth media for up to four weeks. Cultures were examined daily, by light microscopy, for growth and number of microvessels. Apparent microvessels were observed within five days. Confirmation of microvessel identification was by electron microscopy for endothelial cell morphology. There were significantly greater numbers of microvessels at day five and day ten of culture in the pulp explants from orthodontically treated teeth compared with those from the pulps of control teeth. These results are consistent with the hypothesis that there is an increase in angiogenic growth factors in the pulp of orthodontically moved teeth.

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The aim of this study was to determine if diffusible angiogenic growth factors were released in human dental pulp during orthodontic tooth movement. These factors, if diffusible, could induce angiogenesis in other tissues, and may then be isolated and identified. The pulps from 14 premolar teeth treated with straight wire fixed orthodontic appliances for 2 weeks were compared with those of 14 untreated control premolar teeth from the same subjects. Following tooth extraction and sectioning, 1-mm horizontal sections of pulp tissue were embedded in collagen with 1-mm sections of rat aorta and co-cultured in growth media for up to 4 weeks. Sections of rat aorta alone were also cultured. Angiogenic changes in the form of microvessel growth were observed by light microscopy. Microvessel identification was confirmed by electron microscopy and by immunohistochemistry using staining for factor VIII-related antigen marker for endothelial cells. When compared at days 5, 10, and 14 of co-culture, the number of microvessels was significantly greater in the pulps from orthodontically moved teeth than in those from the control teeth. The number of rat aorta microvessels was also significantly greater when co-cultured with pulp from orthodontically moved teeth than with pulp from control teeth and when compared with control cultures of rat aorta alone. There were no significant differences in microvessel numbers between the rat aorta co-cultured with pulp from control teeth and control cultures of rat aorta alone. These results indicate an increase in angiogenic growth factors in the pulp of orthodontically moved teeth, and the enhanced response of the rat aorta when co-cultured with this pulp shows that these factors appear to be diffusible.

This study investigated the role of human epidermal growth factor (EGF) in the angiogenic response of the dental pulp to orthodontic force. The release of angiogenic growth factor EGF in human dental pulp following orthodontic force application was examined using neutralizing antibody anti-human (anti-h) EGF to block its effects. The dental pulps from 10 premolar teeth from 10 patients (equal numbers of males and females aged 11-14 years), treated with a straightwire fixed appliance for 2 weeks and extracted for orthodontic reasons, were divided vertically, and sections from each half-pulp were individually co-cultured with a section of rat aorta in collagen surrounded by growth media. Anti-h EGF was added to the media of the co-cultures from one-half of each pulp from each tooth from each patient; the remaining co-cultures from the other half of each pulp without anti-h EGF were used as the controls. Cultures were examined daily by light microscopy for angiogenic growth and number of microvessels. The addition of anti-h EGF to the growth media in the co-cultures resulted in a significant reduction (P < 0.05, Wilcoxon signed rank test) in pulpal and rat aorta microvessel numbers, compared with the control co-cultures. The results indicate that EGF released following orthodontic force application plays a part in the angiogenic response of the pulp.