{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:11:58Z","timestamp":1790273518526,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T00:00:00Z","timestamp":1659139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Recent studies have revealed that hypoxia alters the PD-L1 expression in periodontal cells. HIF-1\u03b1 is a key regulator for PD-L1. As hypoxia presents a hallmark of an orthodontically induced microenvironment, hypoxic stimulation of PD-L1 expression may play vital roles in immunorthodontics and orthodontically induced inflammatory root resorption (OIIRR). This study aims to investigate the hypoxic regulation of PD-L1 in cementoblasts, and its interaction with hypoxia-induced HIF-1\u03b1 expression. The cementoblast (OCCM-30) cells (M. Somerman, NIH, NIDCR, Bethesda, Maryland) were cultured in the presence and absence of cobalt (II) chloride (CoCl2). Protein expression of PD-L1 and HIF-1\u03b1 as well as their gene expression were evaluated by Western blotting and RT-qPCR. Immunofluorescence was applied to visualize the localization of the proteins within cells. The HIF-1\u03b1 inhibitor (HY-111387, MedChemExpress) was added, and CRISPR\/Cas9 plasmid targeting HIF-1\u03b1 was transferred for further investigation by flow cytometry analysis. Under hypoxic conditions, cementoblasts undergo an up-regulation of PD-L1 expression at protein and mRNA levels. Silencing of HIF-1\u03b1 using CRISPR\/Cas9 indicated a major positive correlation with HIF-1\u03b1 in regulating PD-L1 expression. Taken together, these findings show the influence of hypoxia on PD-L1 expression is modulated in a HIF-1\u03b1 dependent manner. The HIF-1\u03b1\/PD-L1 pathway may play a role in the immune response of cementoblasts. Thus, combined HIF-1\u03b1\/PD-L1 inhibition could be of possible therapeutic relevance for OIIRR prevention.<\/jats:p>","DOI":"10.3390\/cells11152350","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T21:49:02Z","timestamp":1659304142000},"page":"2350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Immunorthodontics: PD-L1, a Novel Immunomodulator in Cementoblasts, Is Regulated by HIF-1\u03b1 under Hypoxia"],"prefix":"10.3390","volume":"11","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, 35392 Giessen, Germany"},{"name":"Department of Periodontology, Faculty of Medicine, Justus Liebig University Giessen, 35392 Giessen, Germany"},{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Gr\u00f6ger","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Faculty of Medicine, Justus Liebig University Giessen, 35392 Giessen, Germany"},{"name":"Department of Periodontology, Faculty of Medicine, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"von Bremen","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Faculty of Medicine, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0495-6926","authenticated-orcid":false,"given":"Joerg","family":"Meyle","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Faculty of Medicine, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Ruf","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Faculty of Medicine, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,30]]},"reference":[{"key":"ref_1","first-page":"54","article-title":"MAPK and \u03b2-Catenin signaling: Implication and interplay in orthodontic tooth movement","volume":"27","author":"Yong","year":"2022","journal-title":"FBL"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1093\/ejo\/cjy007","article-title":"Increased BMI in children-an indicator for less compliance during orthodontic treatment with removable appliances","volume":"40","author":"Lorenz","year":"2018","journal-title":"Eur. 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