Lipid Mediators Derived from Docosahexaenoic Acid Alleviate Periodontal Inflammation and Alveolar Bone Loss in Periodontitis Associated with Suppression of the NF-κB and STAT3 Signaling Pathways.

Background

Lipid mediators (LM), comprising 17S-hydroxy-docosahexaenoic acid, resolvin D5, and protectin DX in a ratio of 3:47:50, were naturally generated from docosahexaenoic acid by soybean lipoxygenase and exhibit potent anti-inflammatory activities. However, their therapeutic potential in periodontitis (PD) remains unclear. Therefore, this study investigated the protective effects of LM against PD in vitro and in vivo.

Methods

Human gingival fibroblasts (HGFs) were stimulated with Porphyromonas gingivalis lipopolysaccharide (PG-LPS) to evaluate the anti-inflammatory effects of LM. Nitric oxide (NO) production, prostaglandin E2 (PGE2) level, inflammatory cytokines secretion, matrix metalloproteinase 9 (MMP9) expression, and NF-κB/STAT3 signaling pathways were analyzed. In vivo, a ligature-induced rat model of PD was established, and LM were orally administered at doses of 5, 10, and 20 μg/kg once daily. The effects of LM were evaluated by histopathological examination, micro-computed tomography (micro-CT), quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC).

Results

In PG-LPS-stimulated HGFs, LM significantly reduced NO and PGE2 production by downregulating inducible nitric oxide synthase and cyclooxygenase-2 expression. Moreover, LM decreased the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-1β, and MMP9, accompanied by suppression of the NF-κB and STAT3 signaling pathways. In the ligature-induced rat model of PD, LM significantly attenuated gingival inflammation and alveolar bone loss. Furthermore, IHC analysis revealed that LM markedly reduced the level of IL-6, TNF-α, MMP9, and phosphorylated STAT3 in gingival tissues.

Conclusions

LM exerted protective effects against periodontitis by alleviating inflammatory response and reducing alveolar bone loss, which may be associated with suppression of the NF-κB and STAT3 signaling pathways.