The molecular mechanism of necroptosis and its correlation with periodontitis

Sun Huanhuan; Zhao Fei; Tao Ran; Liu Bing

doi:10.12307/2025.370

Abstract：BACKGROUND:In recent years,with the deepening of cell death research,necroptosis has gradually become a hot and difficult topic in academic research.Its various signaling pathways and proteins play an important role in the occurrence and development of periodontitis. People try to delay the process of periodontal tissue inflammation by preventing the occurrence of necroptosis. OBJECTIVE:To provide a review on the molecular mechanism of necroptosis and its correlation with periodontitis in the hope of providing new ideas and directions for the prevention,diagnosis,treatment and evaluation of periodontitis. METHODS:The first author searched PubMed,CNKI,and other databases in October 2023 for relevant literature published up to April 2024 with the search terms of "necroptosis,programmed cell death,periodontitis,periodontal,immunity,inflammation,receptor interacting protein kinase 1,receptor interacting protein kinase 3,mixed lineage kinase domain-like" in Chinese and "necroptosis,programmed cell death,periodontitis,periodontal,immunity,inflammation,RIP1,RIP3,MLKL" in English,respectively. The titles and abstracts of each document were read for preliminary screening,and 56 documents were finally selected for generalization and analysis. RESULTS AND CONCLUSION:(1) The main pathogenesis of periodontitis is that periodontal pathogenic bacteria stimulate the organism,leading to changes in the periodontal microenvironment,breaking the original immune balance and releasing a variety of inflammatory factors,triggering an inflammatory response resulting in destruction of periodontal tissues. Necroptosis can modulate the immuno-inflammation in periodontal tissues,thus affecting the development of periodontitis. (2) The occurrence of necroptosis is related to a variety of proteins,signaling pathways,and signaling molecules. Animal experiments have confirmed that the expression of phosphorylated mixed lineage kinase domain-like protein (pMLKL) is related to the degree of inflammation,and RIP3 and pMLKL are highly expressed in the periodontal tissues of mice suffering from periodontitis. Blocking the RIP3/MLKL pathway is conducive to the reduction of inflammation in periodontal tissues and the control of periodontitis progression. (3) To explore whether pMLKL can be used as a diagnostic indicator of periodontitis is of great value in the prevention,diagnosis and treatment of periodontitis.