Journal article

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

Publication year: 2022

Journal: Cells

Volume number: 11

Issue number: 15

eISSN: 2073-4409

Open access status: Gold

DOI Link: https://doi.org/10.3390/cells11152350

Publisher: MDPI

Abstract: 
Recent studies have revealed that hypoxia alters the PD-L1 expression in periodontal cells. HIF-1 alpha 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 alpha 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 alpha 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-l alpha inhibitor (HY-111387, MedChemExpress) was added, and CRISPR/Cas9 plasmid targeting HIF-1 alpha 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 alpha using CRISPR/Cas9 indicated a major positive correlation with HIF-1 alpha in regulating PD-L1 expression. Taken together, these findings show the influence of hypoxia on PD-L1 expression is modulated in a HIF-1 alpha dependent manner. The HIF-1 alpha/PD-L1 pathway may play a role in the immune response of cementoblasts. Thus, combined HIF-1 alpha/PD-L1 inhibition could be of possible therapeutic relevance for OIIRR prevention.

Harvard Citation style: Yong, J., Groeger, S., von Bremen, J., Meyle, J. and Ruf, S. (2022) Immunorthodontics: PD-L1, a Novel Immunomodulator in Cementoblasts, Is Regulated by HIF-1α under Hypoxia, Cells, 11(15), Article 2350. https://doi.org/10.3390/cells11152350

APA Citation style: Yong, J., Groeger, S., von Bremen, J., Meyle, J., & Ruf, S. (2022). Immunorthodontics: PD-L1, a Novel Immunomodulator in Cementoblasts, Is Regulated by HIF-1α under Hypoxia. Cells. 11(15), Article 2350. https://doi.org/10.3390/cells11152350