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Biomedicines
Volume 13
Issue 12
10.3390/biomedicines13123038
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Resolvin D1 Modulates the Inflammatory Processes of Human Periodontal Ligament Cells via NF-κB and MAPK Signaling Pathways

by
Jing Yan
1,
Jiazheng Cai
1,2,
Xiaojing Pan
1,
Si Li
1,
Christopher Graham Fenton
3,
Kristin Andreassen Fenton
2,
Alpdogan Kantarci
4,5,
Yaxin Xue
6,
Ying Xue
7,* and
Zhe Xing
1,2,8,*
1
School/Hospital of Stomatology, Lanzhou University, Lanzhou 730000, China
2
Department of Medical Biology, Faculty of Health Sciences, UiT the Arctic University of Norway, 9037 Tromsø, Norway
3
Genomics Support Centre Tromsø (GSCT), Department of Clinical Medicine, Faculty of Health Sciences, UiT the Arctic University of Norway, 9037 Tromsø, Norway
4
Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA
5
School of Dental Medicine, Harvard University, Boston, MA 02115, USA
6
Computational Biology Unit, Department of Informatics, University of Bergen, 5008 Bergen, Norway
7
Department of Clinical Dentistry, Faculty of Health Sciences, UiT the Arctic University of Norway, 9037 Tromsø, Norway
8
Key Laboratory of Dental Maxillofacial Reconstruction and Biological Intelligence Manufacturing, Lanzhou University, Lanzhou 730000, China
*
Authors to whom correspondence should be addressed.
Biomedicines 2025, 13(12), 3038; https://doi.org/10.3390/biomedicines13123038
Submission received: 24 September 2025 / Revised: 20 November 2025 / Accepted: 8 December 2025 / Published: 10 December 2025
(This article belongs to the Section Cell Biology and Pathology)
Versions Notes

Abstract

Objectives: Periodontitis is a multifactorial inflammatory disease initiated by pathogenic bacteria, such as Porphyromonas gingivalis. Resolvin D1 (RvD1) plays a pivotal role in inflammation resolution. This study aimed to identify the mechanism of the regulatory effects of RvD1 on the inflammatory response of human periodontal ligament cells (hPDLCs). Methods: To investigate the mechanism of RvD1’s impact on the hPDLCs, RNA-sequencing (RNA-seq) was used and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to assess the signaling pathways in which NF-κB and MAPK were determined to play a significant role. Alterations in NF-κB and MAPK pathways were verified by immunofluorescence (IF), quantitative real-time PCR (qRT-PCR), and Western blotting (WB). The expression of RvD1 and lipoxin A4/formyl peptide receptor 2 (ALX/FPR2) was assessed by IF and WB. Inflammatory cytokine interleukin (IL) 6 and IL-1β release was measured by ELISA. Results: GO and KEGG analyses indicated that RvD1 regulates the inflammatory process in PDLCs primarily via TLR4-MyD88-mediated NF-κB and MAPK signaling. RvD1 suppressed lipopolysaccharide (LPS)-induced TLR4 and MyD88 expression, inhibited phosphorylation of NF-κB p65 and its inhibitor IKBKB, and attenuated phosphorylation of p38 MAPK, ERK, and JNK. ALX/FPR2 was expressed on hPDLCs and was further upregulated upon treatment with RvD1. RvD1 significantly down-regulated the IL-6 and IL-1β levels in LPS-stimulated hPDLCs. Conclusions: RvD1 regulates the inflammatory response of LPS-stimulated hPDLCs by the TLR4-MyD88-MAPK and TLR4-MyD88-NF-κB signaling pathways, suggesting the potential role of RvD1 in restoring periodontal tissue homeostasis by regulating PDLC response to inflammatory and infectious stimuli.
Keywords: periodontal ligament cells; Resolvin D1; RNA-seq; NF-κB; MAPK periodontal ligament cells; Resolvin D1; RNA-seq; NF-κB; MAPK

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MDPI and ACS Style

Yan, J.; Cai, J.; Pan, X.; Li, S.; Fenton, C.G.; Fenton, K.A.; Kantarci, A.; Xue, Y.; Xue, Y.; Xing, Z. Resolvin D1 Modulates the Inflammatory Processes of Human Periodontal Ligament Cells via NF-κB and MAPK Signaling Pathways. Biomedicines 2025, 13, 3038. https://doi.org/10.3390/biomedicines13123038

AMA Style

Yan J, Cai J, Pan X, Li S, Fenton CG, Fenton KA, Kantarci A, Xue Y, Xue Y, Xing Z. Resolvin D1 Modulates the Inflammatory Processes of Human Periodontal Ligament Cells via NF-κB and MAPK Signaling Pathways. Biomedicines. 2025; 13(12):3038. https://doi.org/10.3390/biomedicines13123038

Chicago/Turabian Style

Yan, Jing, Jiazheng Cai, Xiaojing Pan, Si Li, Christopher Graham Fenton, Kristin Andreassen Fenton, Alpdogan Kantarci, Yaxin Xue, Ying Xue, and Zhe Xing. 2025. "Resolvin D1 Modulates the Inflammatory Processes of Human Periodontal Ligament Cells via NF-κB and MAPK Signaling Pathways" Biomedicines 13, no. 12: 3038. https://doi.org/10.3390/biomedicines13123038

APA Style

Yan, J., Cai, J., Pan, X., Li, S., Fenton, C. G., Fenton, K. A., Kantarci, A., Xue, Y., Xue, Y., & Xing, Z. (2025). Resolvin D1 Modulates the Inflammatory Processes of Human Periodontal Ligament Cells via NF-κB and MAPK Signaling Pathways. Biomedicines, 13(12), 3038. https://doi.org/10.3390/biomedicines13123038

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