IADR Abstract Archives
Regulation of Macrophage Differentiation by p53 Affects the Progression of Periodontitis
Objectives: Little evidence has demonstrated the relationship between p53 gene and periodontitis. This study aims to investigate whether p53 influences the progression of periodontitis by regulating the differentiation of macrophages.
Methods: Firstly, the differentiation of RAW264.7 and BMDM pretreated with p53 inhibitors or activators were observed by flow cytometry, followed the expression and secretion of cytokines were detected by qRT-PCR, and ELISA in vitro. Then, the severity of periodontitis, levels of gene expression and secretion of inflammatory factors were measured by histological stains and molecular biological methods in mice with experimental periodontitis treated with p53 inhibitors or activators. Further, the periodontal inflammation was compared between p53-KO mice and wild-type mice.
Results: The in vitro results showed that the p53 gene only affected the differentiation of macrophages to M1-type under inflammatory stimulation, not in resting status. Both in vivo and in vitro experiments demonstrated that the expression and secretion of inflammatory cytokines (IL-6, TNF-a and IL-10) were promoted by p53 inhibitors, but inhibited by the p53 activators. Meanwhile, mice with experimental periodontitis exhibited worse periodontitis after treated with p53 inhibitors. Furthermore, compared to wild-type mice, p53-KO mice exhibited a more intense response to periodontal stimulation and had higher levels of gene expression and secretion of inflammatory factors.
Conclusions: Activation of p53 impairs the ability of macrophages to differentiate towards the inflammatory M1-type and relieves periodontitis, which provides novel insights that activation of p53 might contribute to the treatment of periodontitis.
Methods: Firstly, the differentiation of RAW264.7 and BMDM pretreated with p53 inhibitors or activators were observed by flow cytometry, followed the expression and secretion of cytokines were detected by qRT-PCR, and ELISA in vitro. Then, the severity of periodontitis, levels of gene expression and secretion of inflammatory factors were measured by histological stains and molecular biological methods in mice with experimental periodontitis treated with p53 inhibitors or activators. Further, the periodontal inflammation was compared between p53-KO mice and wild-type mice.
Results: The in vitro results showed that the p53 gene only affected the differentiation of macrophages to M1-type under inflammatory stimulation, not in resting status. Both in vivo and in vitro experiments demonstrated that the expression and secretion of inflammatory cytokines (IL-6, TNF-a and IL-10) were promoted by p53 inhibitors, but inhibited by the p53 activators. Meanwhile, mice with experimental periodontitis exhibited worse periodontitis after treated with p53 inhibitors. Furthermore, compared to wild-type mice, p53-KO mice exhibited a more intense response to periodontal stimulation and had higher levels of gene expression and secretion of inflammatory factors.
Conclusions: Activation of p53 impairs the ability of macrophages to differentiate towards the inflammatory M1-type and relieves periodontitis, which provides novel insights that activation of p53 might contribute to the treatment of periodontitis.