Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs  

作　　者：Yushang Wang Lihua Wang Tianyong Sun Song Shen Zixuan Li Xiaomei Ma Xiufeng Gu Xiumei Zhang Ai Peng Xin Xu Qiang Feng 

机构地区：[1]Department of Implantology,School and Hospital of Stomatology,Cheeloo College of Medicine,Shandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration,Jinan,China [2]Department of Human Microbiome,School and Hospital of Stomatology,Cheeloo College of Medicine,Shandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration,Jinan,China [3]Department of Orthodontics,School and Hospital of Stomatology,Cheeloo College of Medicine,Shandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration,Jinan,China [4]State key laboratory of microbial technology,Shandong University,Qingdao,China

出　　处：《International Journal of Oral Science》2023年第1期113-126,共14页国际口腔科学杂志（英文版）

基　　金：foundation support of the National Natural Science Foundation of China(Grant No.82071122);the Program of Taishan Young from Shandong Province;Major Innovation Projects in Shandong Province(No.2021SFGC0502);Oral Microbiome Innovation Team of Young Scientist Project of Shandong Province(Grant No.2020KJK001)and Jinan City(2021GXRC021);The National High-level Young Scientist Project Foundation(2019);Excellent Young Scientist Foundation of Shandong Province(Grant No.ZR202102230369)。

摘　　要：Fusobacterium nucleatum(F.nucleatum)is an early pathogenic colonizer in periodontitis,but the host response to infection with this pathogen remains unclear.In this study,we built an F.nucleatum infectious model with human periodontal ligament stem cells(PDLSCs)and showed that F.nucleatum could inhibit proliferation,and facilitate apoptosis,ferroptosis,and inflammatory cytokine production in a dose-dependent manner.The F.nucleatum adhesin Fad A acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β,IL-6 and IL-8.Further study showed that Fad A could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways.Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F.nucleatum infection.NFκB1 and NFκB2 upregulated after 3 h of F.nucleatum-infection,and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time.Using computational drug repositioning analysis,we predicted and validated that two potential drugs(piperlongumine and fisetin)could attenuate the negative effects of F.nucleatum-infection.Collectively,this study unveils the potential pathogenic mechanisms of F.nucleatum and the host inflammatory response at the early stage of F.nucleatum infection.

关 键 词：INFLAMMATORY DRUGS PDL 

分 类 号：R781.42[医药卫生—口腔医学]