Genetically engineered M2-like macrophage-derived exosomes for ***-suppressed cementum regeneration:From mechanism to therapy
作者机构:State Key Laboratory of Oral&Maxillofacial Reconstruction and RegenerationKey Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanChina Department of PeriodontologySchool&Hospital of StomatologyWuhan UniversityWuhanChina
出 版 物:《Bioactive Materials》 (生物活性材料(英文))
年 卷 期:2024年第32卷第2期
页 面:473-487页
核心收录:
学科分类:0831[工学-生物医学工程(可授工学、理学、医学学位)] 08[工学] 0836[工学-生物工程]
基 金:supported by the National Natural Science Foundation of China(No.82370967 No.82170963)
主 题:Casein kinase 2 interacting protein-1 M2 macrophage Exosome Cementum regeneration Porphyromonas gingivalis
摘 要:Cementum,a thin layer of mineralized tissue covering tooth root surface,is recognized as the golden standard in periodontal ***,current efforts mainly focus on alveolar bone regeneration rather than cementum regeneration,and rarely take Porphyromonas gingivalis(Pg),the keystone pathogen responsible for periodontal tissue destruction,into *** M2 macrophage-derived exosomes(M2-EXO)show promise in tissue regeneration,the exosome-producing M2 macrophages are induced by exogenous cytokines with transitory and unstable effects,restricting the regeneration potential of ***,exosomes derived from genetically engineered M2-like macrophages are constructed by silencing of casein kinase 2 interacting protein-1(Ckip-1),a versatile player involved in various biological ***-1 silencing is proved to be an effective gene regulation strategy to obtain permanent M2-like macrophages with mineralization-promoting ***,exosomes derived from Ckip-1-silenced macrophages(sh-Ckip-1-EXO)rescue Pg-suppressed cementoblast mineralization and ***,sh-Ckip-1-EXO delivers Let-7f-5p targeting and silencing Ckip-1,a negative regulator also for cementum formation and cementoblast *** deeply,downregulation of Ckip-1 in cementoblasts by exosomal Let-7f-5p activates PGC-1α-dependent mitochondrial *** all,this study provides a new strategy of genetically engineered M2-like macrophage-derived exosomes for cementum regeneration under Pg-dominated inflammation.