VEGFR-2 Reduces While Combined VEGFR-2 and -3 Signaling Increases Inflammation in Apical Periodontitis

Overview

Journal J Oral Microbiol

Specialty Dentistry

Date 2016 Sep 22

PMID 27650043

Citations 3

Authors

Anca Virtej

Panagiota Papadakou

Hajime Sasaki

Athanasia Bletsa

Ellen Berggreen

Affiliations

Soon will be listed here.

Abstract

Background: In apical periodontitis, oral pathogens provoke an inflammatory response in the apical area that induces bone resorptive lesions. In inflammation, angio- and lymphangiogenesis take place. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key players in these processes and are expressed in immune cells and endothelial cells in the lesions.

Objective: We aimed at testing the role of VEGFR-2 and -3 in periapical lesion development and investigated their role in lymphangiogenesis in the draining lymph nodes.

Design: We induced lesions by pulp exposure in the lower first molars of C57BL/6 mice. The mice received IgG injections or blocking antibodies against VEGFR-2 (anti-R2), VEGFR-3 (anti-R3), or combined VEGFR-2 and -3, starting on day 0 until day 10 or 21 post-exposure.

Results: Lesions developed faster in the anti-R2 and anti-R3 group than in the control and anti-R2/R3 groups. In the anti-R2 group, a strong inflammatory response was found expressed as increased number of neutrophils and osteoclasts. A decreased level of pro-inflammatory cytokines was found in the anti-R2/R3 group. Lymphangiogenesis in the draining lymph nodes was inhibited after blocking of VEGFR-2 and/or -3, while the largest lymph node size was seen after anti-R2 treatment.

Conclusions: We demonstrate an anti-inflammatory effect of VEGFR-2 signaling in periapical lesions which seems to involve neutrophil regulation and is independent of angiogenesis. Combined signaling of VEGFR-2 and -3 has a pro-inflammatory effect. Lymph node lymphangiogenesis is promoted through activation of VEGFR-2 and/or VEGFR-3.

Citing Articles

Protective Actions in Apical Periodontitis: The Regenerative Bioactivities Led by Mesenchymal Stem Cells.

Lyu P, Song Y, Bi R, Li Z, Wei Y, Huang Q Biomolecules. 2022; 12(12).

PMID: 36551165 PMC: 9776067. DOI: 10.3390/biom12121737.

Vascular Endothelial Growth Factor: A Translational View in Oral Non-Communicable Diseases.

Niklander S, Bordagaray M, Fernandez A, Hernandez M Biomolecules. 2021; 11(1).

PMID: 33445558 PMC: 7826734. DOI: 10.3390/biom11010085.

Activation of hypoxia-inducible factor 1 attenuates periapical inflammation and bone loss.

Hirai K, Furusho H, Hirota K, Sasaki H Int J Oral Sci. 2018; 10(2):12.

PMID: 29654284 PMC: 5966812. DOI: 10.1038/s41368-018-0015-0.

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