Journal article

Authors list: Yong, Jiawen; Groeger, Sabine; Meyle, Joerg; Ruf, Sabine

Publication year: 2022

Journal: International Journal of Molecular Sciences

Volume number: 23

Issue number: 13

eISSN: 1422-0067

Open access status: Gold

DOI Link: https://doi.org/10.3390/ijms23136977

Publisher: MDPI

Abstract: 
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)-1 alpha 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-1 alpha as well as their gene expression. Immunofluorescence was applied to visualize the localization of these proteins within cells. An HIF-1 alpha 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-1 alpha inhibited the P. gingivalis PGN-inducible PD-L1 protein expression under compression, indicating an HIF-1 alpha dependent regulation of PD-L1 induction. Concomitantly, an HIF-1 alpha 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-1 alpha dependently. In this regard, HIF-1 alpha 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.

Harvard Citation style: Yong, J., Groeger, S., Meyle, J. and Ruf, S. (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(13), Article 6977. https://doi.org/10.3390/ijms23136977

APA Citation style: Yong, J., Groeger, S., Meyle, J., & Ruf, S. (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(13), Article 6977. https://doi.org/10.3390/ijms23136977