Annexin A1 protects periodontal ligament cells against lipopolysaccharide-induced inflammatory response and cellular senescence: An implication in periodontitis.

Abstract

Periodontitis is an inflammatory condition that affects the tooth-supporting structures, triggered by the host's immune response toward the bacterial deposits around the teeth. Annexin A1 (AnxA1), a vital member of the annexin superfamily, is known for its diverse physiological functions, particularly its anti-inflammatory and anti-senescence properties. We hypothesized that AnxA1 has a protective effect against lipopolysaccharide (LPS)-induced inflammatory responses and cellular damage in periodontal ligament cells (PDLCs). In this study, we demonstrate that LPS stimulation significantly reduced telomerase activity in PDLCs, a decline that was dose-dependently reversed by AnxA1. Importantly, AnxA1 protected the cells from LPS-induced cellular senescence and the downregulation of human telomerase reverse transcriptase (hTERT) expression. In line with this, AnxA1 suppressed the LPS-induced expression of p21 and p16 at both the mRNA and protein levels. Furthermore, AnxA1 demonstrated potent anti-inflammatory effects by inhibiting the secretion of interleukin 6 (IL-6), interleukin 8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1). It also mitigated LPS-induced oxidative stress by reducing the levels of phosphorylated Foxo3a (Ser253) and restored sirtuin 1 (SIRT1) expression. Notably, SIRT1 silencing abolished AnxA1's protective effects on Foxo3a phosphorylation and cellular senescence, suggesting that SIRT1 mediates AnxA1's actions. In conclusion, AnxA1 protected PDLCs against LPS-triggered inflammation and cell senescence by activating SIRT1 signal pathway. These findings indicate that AnxA1 could serve as a promising therapeutic strategy for the treatment of periodontitis.