Impact of Resolvin D1 on the inflammatory phenotype of periodontal ligament cell response to hypoxia. (9th August 2022)

• Record Type: Journal Article
• Authors: Cai, Jiazheng; Liu, Jing; Yan, Jing; Lu, Xuexia; Wang, Xiaoli; Li, Si; Mustafa, Kamal; Wang, Huihui; Xue, Ying; Mustafa, Manal; Kantarci, Alpdogan; Xing, Zhe
• Is Part Of: Journal of periodontal research. Volume 57:Number 5(2022)
• Page Start: 1034
• Page End: 1042
• Publication Date: 2022-08-09
• Subjects: hypoxia -- osteogenesis -- periodontal ligament cells -- pro‐inflammatory phenotype -- Resolvin D1; Periodontics -- Periodicals; 617.632
• DOI: 10.1111/jre.13044
• Languages: English
• ISSNs: 0022-3484

Abstract

Abstract: Objective: Periodontal ligament cells (PDLCs) are critical for wound healing and regenerative capacity of periodontal diseases. Within an inflammatory periodontal pocket, a hypoxic environment can aggravate periodontal inflammation, where PDLCs response to the inflammation would change. Resolvin D1 (RvD1) is an endogenous lipid mediator, which can impact intracellular inflammatory pathways of periodontal/oral cells and periodontal regeneration. It is not clear how hypoxia and RvD1 impact the inflammatory responses of pro‐inflammatory PDLCs phenotype. Therefore, this study aimed to test hypoxia could induce changes in pro‐inflammatory phenotype of PDLCs and RvD1 could reverse it. Methods: Human PDLCs were cultured from periodontal tissues from eight healthy individuals and were characterized by immunofluorescence staining of vimentin and cytokeratin. Cell viability was examined by Methyl‐thiazolyl‐tetrazolium (MTT) assay. To examine the effects of hypoxia and RvD1 on the inflammatory responses of pro‐inflammatory PDLCs phenotype, protein levels and gene expressions of inflammatory cytokines and signal transduction molecules were measured by enzyme‐linked immunosorbent assay (ELISA), western blotting (WB), and real‐time quantitative reverse transcription PCR (real‐time qRT‐PCR). Alizarin red S staining and real‐time qRT‐PCR were employed to study the effects of hypoxia and RvD1 on the osteogenic differentiation of pro‐inflammatory PDLCs phenotype. Results: It was found that hypoxia increases the expression of inflammatory factors at the gene level ( p < . 05 ). RvD1 reduced the expression of IL‐1β ( p < . 05 ) in PDLCs under hypoxia both at the protein and RNA levels. There were increases in the expression of p38 mitogen‐activated protein kinase (p38 MAPK, p < . 01 ) and protein kinase B (Akt, p < . 05) in response to RvD1. Also, a significantly higher density of calcified nodules was observed after treatment with RvD1 for 21 days under hypoxia. Conclusion: Our results indicate that hypoxia up‐regulated the inflammatory level of PDLCs. RvD1 can reduce under‐hypoxia‐induced pro‐inflammatory cytokines in the inflammatory phenotype of PDLCs. Moreover, RvD1 promotes the calcium nodules in PDLCs, possibly by affecting the p38 MAPK signaling pathway through Akt and HIF‐1α.