Resolvin E1 and maresin 1 restore senescence-induced disruption of human periodontal ligament fibroblast function

Background: Aging impairs the mechanisms that regulate inflammation, resulting in low-level chronic inflammation even in the absence of infection and increasing the risk of developing age-related illnesses. Periodontal ligament fibroblasts (PDLF) are responsible for wound healing and periodontal tissue regeneration. Periodontal inflammation disrupts PDLF function, which may be exacerbated by aging. We tested the hypothesis that senescence-induced changes in PDLF will be reversed by specialized mediators of resolution of inflammation-resolvin E1 (RvE1) and maresin 1 (MaR1). Methods: Primary human PDLFs were cultured with D-galactose to induce senescence. The senescence was confirmed with a senescence-associated beta-galactosidase assay. The impact of senescence on cell viability, proliferation, wound healing, cell cycle, type I collagen expression, oxidative stress, inflammatory profiles, and growth factor production was evaluated. We measured the specialized pro-resolving mediators (SPM)-mediated effects on senescent PDL fibroblasts by treating them with 100 nM RvE1 or 100 nM MaR1 or the vehicle. Results: D-galactose treatment significantly increased senescence, oxidative stress, and inflammation while it delayed wound closure and reduced cell viability and proliferation on PDLFs (p < 0.05). RvE1 or MaR1 treatment significantly decreased β-galactosidase expression and inflammation, restored cell viability, increased cell proliferation, and accelerated wound closure (p < 0.05). MaR1 demonstrated a more potent impact on reversing the senescence and regenerative effect than RvE1. Conclusion: RvE1 and MaR1 reversed the senescence-induced changes in primary PDLFs, restoring wound healing capacity and function. Plain Language Summary: Aging may induce periodontal inflammation, which interferes with the activity of the periodontal ligament fibroblasts (PDLFs). We measured the effect of specific mediators of resolution of inflammation, resolvin E1 (RvE1) and maresin 1 (MaR1), on aging in PDLFs. Treatment with RvE1 or MaR1 significantly reduced inflammation and senescence and restored cell proliferation, wound closure, and cell viability.