Resolvin D1 modulates periodontal ligament fibroblast function

J Periodontol. 2023 May;94(5):683-693. doi: 10.1002/JPER.22-0462. Epub 2022 Dec 20.


Background: The resolution of inflammation is an active process mediated by specialized lipid mediators called lipoxins and resolvins. Periodontal ligament fibroblasts (PDLFs) play a significant role in periodontal regeneration. The purpose of the current study was to determine the impact of resolvin D1 (RvD1) on human PDLF cell wound healing and proliferation, receptor expression (G-protein-coupled receptor 32 [GPR32] and formyl peptide receptor 2 [ALX/FPR2]), and cytokine expression and release.

Methods: PDLFs were stimulated with interleukin-1β (IL-1β) (500 pg/ml) with and without RvD1 (100 nM). RvD1 receptor expression was determined by quantitative real-time polymerase chain reaction (qPCR), immunofluorescence microscopy, and fluorescence-activated cell sorting. Wound closure was measured by a scratch assay, and proliferation was determined by bromodeoxyuridine incorporation. Interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1, cyclooxygenase-2, matrix metalloproteinases-1, -2, and -3 (MMP-1, -2, and -3), tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1 and -2), prostaglandin E2, and osteoprotegerin (OPG) gene expression and production were measured using qPCR and Western blotting, multiplex immunoassay, and enzyme-linked immunosorbent assay.

Results: PDLF expressed GPR32 and ALX/FPR2. RvD1 reversed IL-1β-induced inhibition of wound healing and proliferation of PDLF. IL-1β also induced the production of proinflammatory cytokines and MMPs. This effect was reversed by RvD1. RvD1 reversed IL-1β-induced inhibition of TIMP-1, TIMP-2, and OPG.

Conclusion: The data suggested that RvD1 has a pro-wound healing, proliferative, and anti-inflammatory impact on the PDLF that favors periodontal regeneration.

Keywords: aspirin-triggered resolvin D1; cytokine; fibroblast; inflammation; periodontal disease; regeneration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cytokines
  • Docosahexaenoic Acids / pharmacology
  • Fibroblasts
  • Humans
  • Inflammation
  • Periodontal Ligament* / metabolism
  • Tissue Inhibitor of Metalloproteinase-1*


  • resolvin D1
  • Tissue Inhibitor of Metalloproteinase-1
  • Docosahexaenoic Acids
  • Cytokines