{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T20:30:24Z","timestamp":1767904224231,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u03b1 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\u03b1 as well as their gene expression. Immunofluorescence was applied to visualize the localization of these proteins within cells. An HIF-1\u03b1 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\u03b1 inhibited the P. gingivalis PGN-inducible PD-L1 protein expression under compression, indicating an HIF-1\u03b1 dependent regulation of PD-L1 induction. Concomitantly, an HIF-1\u03b1 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\u03b1 dependently. In this regard, HIF-1\u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms23136977","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T21:25:00Z","timestamp":1656019500000},"page":"6977","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Immunorthodontics: Role of HIF-1\u03b1 in the Regulation of (Peptidoglycan-Induced) PD-L1 Expression in Cementoblasts under Compressive Force"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3021-075X","authenticated-orcid":false,"given":"Jiawen","family":"Yong","sequence":"first","affiliation":[{"name":"Department of Orthodontics, Faculty of Medicine, Justus Liebig University Giessen, D-35392 Giessen, Germany"},{"name":"Department of Periodontology, Faculty of Medicine, Justus Liebig University Giessen, D-35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Gr\u00f6ger","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Faculty of Medicine, Justus Liebig University Giessen, D-35392 Giessen, Germany"},{"name":"Department of Periodontology, Faculty of Medicine, Justus Liebig University Giessen, D-35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg","family":"Meyle","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Faculty of Medicine, Justus Liebig University Giessen, D-35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Ruf","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Faculty of Medicine, Justus Liebig University Giessen, D-35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"645005","DOI":"10.3389\/fcell.2021.645005","article-title":"Adiponectin as well as compressive forces regulate in vitro beta-catenin expression on cementoblasts via mitogen-activated protein kinase signaling activation","volume":"9","author":"Yong","year":"2021","journal-title":"Front. 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