Expression and Function of Hypoxia Inducible Factor-1α and Vascular Endothelial Growth Factor in Pulp Tissue of Teeth under Orthodontic Movement

Fulan Wei, Shuangyan Yang, Hui Xu, Qingyuan Guo, Qi Li, Lihua Hu, Dongxu Liu, Chunling Wang, Fulan Wei, Shuangyan Yang, Hui Xu, Qingyuan Guo, Qi Li, Lihua Hu, Dongxu Liu, Chunling Wang

Abstract

Orthodontic force may lead to cell damage, circulatory disturbances, and vascular changes of the dental pulp, which make a hypoxic environment in pulp. In order to maintain the homeostasis of dental pulp, hypoxia will inevitably induce the defensive reaction. However, this is a complex process and is regulated by numerous factors. In this study, we established an experimental animal model of orthodontic tooth movement to investigate the effects of mechanical force on the expression of VEGF and HIF-1α in dental pulp. Histological analysis of dental pulp and expressions of HIF-1α and VEGF proteins in dental pulp were examined. The results showed that inflammation and vascular changes happened in dental pulp tissue in different periods. Additionally, there were significant changes in the expression of HIF-1α and VEGF proteins under orthodontic force. After application of mechanical load, expression of HIF-1α and VEGF was markedly positive in 1, 3, 7 d, and 2 w groups, and then it weakened in 4 w group. These findings suggested that the expression of HIF-1α and VEGF was enhanced by mechanical force. HIF-1α and VEGF may play an important role in retaining the homeostasis of dental pulp during orthodontic tooth movement.

Figures

Figure 1
Figure 1
Photomicrograph of histological section of the dental pulp for different time periods. (a) Showing the control group: 1 = odontoblastic layer; 2 = Weil zone (cell-free zone); 3 = cell-rich zone; 4 = central pulp area. (b) Photomicrograph of a histological section showing in detail the odontoblastic layer of the dental pulp of the 1 d group. White arrows indicate the inflammatory cells; black arrows indicate the areas of congested vessels. (c) Photomicrograph of a histological section showing areas of congested vessels and edema in the pulp center of the 3 d group. Arrows indicate the areas of congested vessels. (d) Photomicrograph of a histological section showing areas of congested vessels and edema in the pulp center of the 7 d group. Arrows indicate the congested vessels. (e) Photomicrograph showing the vascularization of the central layer of the pulp of the 2 w group. Arrows indicate the vessels. (f) Photomicrograph showing blood cells inside the vessels of the pulp of the 4 w group (images on the left: magnification ×200, bar = 100 μm; images on the right: magnification ×1000).
Figure 2
Figure 2
Immunohistochemistry analysis of HIF-1α protein expression in rat dental pulp tissue after orthodontic force. HIF-1α protein was weakly stained in control group (a). (b–e) HIF-1α protein expression became strongly stained after 1, 3, and 7 d of orthodontic force and reached the peak level at 2 w group. Then HIF-1α protein expression weakened in the 4 w group but was still higher than the control group (f). Arrows indicate the vessel wall (images on the left: magnification ×200, bar = 100 μm; images on the right: magnification ×1000).
Figure 3
Figure 3
Immunohistochemistry analysis of VEGF protein expression in rat dental pulp tissue after orthodontic force. VEGF protein was weakly stained in control group (a). VEGF protein became slightly stained after 1 d of orthodontic force (b). (c–e) VEGF protein expression became positively stained after 3 d, 7 d, and 2 w after orthodontic force and also reached the peak level at 2 w group. VEGF protein expression then declined in the 4 w group (f). Arrows indicate the vessel wall (images on the left: magnification ×200, bar = 100 μm; images on the right: magnification ×1000).

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