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Annexin A1 (AnxA1), a vital member of the annexin superfamily, is known for its diverse physiological functions, particularly its anti\u2010inflammatory and anti\u2010senescence properties. We hypothesized that AnxA1 has a protective effect against lipopolysaccharide (LPS)\u2010induced 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\u2010dependently reversed by AnxA1. Importantly, AnxA1 protected the cells from LPS\u2010induced cellular senescence and the downregulation of human telomerase reverse transcriptase (hTERT) expression. In line with this, AnxA1 suppressed the LPS\u2010induced expression of p21 and p16 at both the mRNA and protein levels. Furthermore, AnxA1 demonstrated potent anti\u2010inflammatory effects by inhibiting the secretion of interleukin 6 (IL\u20106), interleukin 8 (IL\u20108), and monocyte chemoattractant protein\u20101 (MCP\u20101). It also mitigated LPS\u2010induced 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\u2010triggered 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.<\/jats:p>","DOI":"10.1002\/bab.2675","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T07:22:12Z","timestamp":1727248932000},"page":"449-459","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Annexin A1 protects periodontal ligament cells against lipopolysaccharide\u2010induced inflammatory response and cellular senescence: An implication in periodontitis"],"prefix":"10.1002","volume":"72","author":[{"given":"Shuwen","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Stomatology Henan Provincial People's Hospital, Zhengzhou University People's Hospital  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stomatology Henan 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