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Article

Immunorthodontics: Role of HIF-1α in the Regulation of (Peptidoglycan-Induced) PD-L1 Expression in Cementoblasts under Compressive Force

by 1,2,*,†, 1,2,†, 2 and 1
1
Department of Orthodontics, Faculty of Medicine, Justus Liebig University Giessen, D-35392 Giessen, Germany
2
Department of Periodontology, Faculty of Medicine, Justus Liebig University Giessen, D-35392 Giessen, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Christopher W Cutler
Int. J. Mol. Sci. 2022, 23(13), 6977; https://doi.org/10.3390/ijms23136977
Received: 17 May 2022 / Revised: 8 June 2022 / Accepted: 22 June 2022 / Published: 23 June 2022
(This article belongs to the Special Issue Immune Cell Regulation during Inflammatory Responses)
Patients with periodontitis undergoing orthodontic therapy may suffer from undesired dental root resorption. The purpose of this in vitro study was to investigate the molecular mechanisms resulting in PD-L1 expression of cementoblasts in response to infection with Porphyromonas gingivalis (P. gingivalis) peptidoglycan (PGN) and compressive force (CF), and its interaction with hypoxia-inducible factor (HIF)-1α molecule: The cementoblast (OCCM-30) cells were kinetically infected with various concentrations of P. gingivalis PGN in the presence and absence of CF. Western blotting and RT-qPCR were performed to examine the protein expression of PD-L1 and HIF-1α as well as their gene expression. Immunofluorescence was applied to visualize the localization of these proteins within cells. An HIF-1α inhibitor was added for further investigation of necroptosis by flow cytometry analysis. Releases of soluble GAS-6 were measured by ELISA. P. gingivalis PGN dose dependently stimulated PD-L1 upregulation in cementoblasts at protein and mRNA levels. CF combined with P. gingivalis PGN had synergistic effects on the induction of PD-L1. Blockade of HIF-1α inhibited the P. gingivalis PGN-inducible PD-L1 protein expression under compression, indicating an HIF-1α dependent regulation of PD-L1 induction. Concomitantly, an HIF-1α inhibitor decreased the GAS-6 release in the presence of CF and P. gingivalis PGN co-stimulation. The data suggest that PGN of P. gingivalis participates in PD-L1 up-regulation in cementoblasts. Additionally, the influence of compressive force on P. gingivalis PGN-induced PD-L1 expression occurs in HIF-1α dependently. In this regard, HIF-1α may play roles in the immune response of cementoblasts via immune-inhibitory PD-L1. Our results underline the importance of molecular mechanisms involved in bacteria-induced periodontics and root resorption. View Full-Text
Keywords: Porphyromonas gingivalis; peptidoglycan; cementoblasts; HIF-1α; PD-L1; immunorthodontics Porphyromonas gingivalis; peptidoglycan; cementoblasts; HIF-1α; PD-L1; immunorthodontics
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MDPI and ACS Style

Yong, J.; Gröger, S.; Meyle, J.; Ruf, S. Immunorthodontics: Role of HIF-1α in the Regulation of (Peptidoglycan-Induced) PD-L1 Expression in Cementoblasts under Compressive Force. Int. J. Mol. Sci. 2022, 23, 6977. https://doi.org/10.3390/ijms23136977

AMA Style

Yong J, Gröger S, Meyle J, Ruf S. Immunorthodontics: Role of HIF-1α in the Regulation of (Peptidoglycan-Induced) PD-L1 Expression in Cementoblasts under Compressive Force. International Journal of Molecular Sciences. 2022; 23(13):6977. https://doi.org/10.3390/ijms23136977

Chicago/Turabian Style

Yong, Jiawen, Sabine Gröger, Joerg Meyle, and Sabine Ruf. 2022. "Immunorthodontics: Role of HIF-1α in the Regulation of (Peptidoglycan-Induced) PD-L1 Expression in Cementoblasts under Compressive Force" International Journal of Molecular Sciences 23, no. 13: 6977. https://doi.org/10.3390/ijms23136977

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