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The differentiation and the inflammatory cytokines (TNF-\u03b1 and IL-6) expression of THP-1, RAW264.7 and bone marrow derived macrophage (BMDM) cells, treating with Pifithrin-\u03b1 (P53 inhibitor) or Nutlin-3a (P53 activator) under lipopolysaccharide (LPS) stimulation, were observed by flow cytometry, qPCR and ELISA. The severity of periodontitis, inflammatory cytokines expression and macrophages infiltration were measured in experimental periodontitis wild-type mice and <jats:italic>p53<\/jats:italic> gene conditional knocked-out (<jats:italic>p53<\/jats:italic>-CKO) mice, which were established by ligation and LPS injection. A higher number of P53-positive macrophages was found infiltrated in periodontitis tissues. <jats:italic>In vitro<\/jats:italic> experiments showed that compared with Nutlin-3a, the proportion of M1-type macrophages and the expression of TNF-\u03b1 and IL-6 were higher in Pifithrin-\u03b1 treated cells under LPS stimulation. <jats:italic>In vivo<\/jats:italic> experimental periodontitis mice, the Pifithrin-\u03b1 intraperitoneal injection group showed greater alveolar bone loss, higher levels of TNF-\u03b1 and IL-6 secretion and more M1-type macrophages infiltration, while the Nutlin-3a intraperitoneal injection group were observed mild symptoms compared with mice in the periodontitis group. <jats:italic>P53<\/jats:italic>-CKO mice exhibited more severe periodontitis and more M1-type macrophages infiltrated in local tissues compared with wild-type mice. The activation of <jats:italic>p53<\/jats:italic> gene could alleviate periodontitis by reducing M1-type macrophage polarization. P53 may serve as keeper in the progression of periodontitis, providing new insights into periodontitis treatment.<\/jats:p>","DOI":"10.1007\/s10753-024-01968-w","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T15:03:15Z","timestamp":1707231795000},"page":"1170-1184","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["P53 Alleviates the Progression of Periodontitis by Reducing M1-type Macrophage Differentiation"],"prefix":"10.1007","volume":"47","author":[{"given":"Tingting","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongru","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaolei","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dikan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanzi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqing","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,6]]},"reference":[{"issue":"6","key":"1968_CR1","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.3390\/ijms20061414","volume":"20","author":"D Liccardo","year":"2019","unstructured":"Liccardo, D., A. 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