Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure  

作　　者：Wanhao Yan Xiao Lin Yiqian Ying Jun Li Zhipeng Fan 

机构地区：[1]Laboratory of Molecular Signaling and Stem Cells Therapy,Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction,Capital Medical University School of Stomatology,Beijing,China [2]Department of Dental Implant Center,Beijing Stomatological Hospital,School of Stomatology,Capital Medical University,Beijing,China [3]Department of Oral Implantology,Tianjin Stomatological Hospital,School of Medicine,Nankai University,Tianjin,China [4]Research Unit of Tooth Development and Regeneration,Chinese Academy of Medical Sciences,Beijing,China

出　　处：《International Journal of Oral Science》2023年第1期50-62,共13页国际口腔科学杂志（英文版）

基　　金：supported by grants from the Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(NO.CXTD202204 to Z.P.F.);the CAMS Innovation Fund for Medical Sciences(2019-I2 M-5-031 to Z.P.F.);the National Natural Science Foundation of China(82000998 to X.L.)。

摘　　要：The failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus(T2DM)is higher than that in nondiabetic patients.This due,in part,to the impaired function of bone marrow mesenchymal stem cells(BMSCs)from the jawbone marrow of T2DM patients(DM-BMSCs),limiting implant osseointegration.RNA N6-methyladenine(m6A)is important for BMSC function and diabetes regulation.However,it remains unclear how to best regulate m6A modifications in DM-BMSCs to enhance function.Based on the“m6A site methylation stoichiometry”of m6A single nucleotide arrays,we identified 834 differential m6Amethylated genes in DM-BMSCs compared with normal-BMSCs(N-BMSCs),including 43 and 790 m6A hypermethylated and hypomethylated genes,respectively,and 1 gene containing hyper-and hypomethylated m6A sites.Differential m6A hypermethylated sites were primarily distributed in the coding sequence,while hypomethylated sites were mainly in the 3’-untranslated region.The largest and smallest proportions of m6A-methylated genes were on chromosome 1 and 21,respectively.Maz F-PCR and real-time RTPCR results for the validation of erythrocyte membrane protein band 4.1 like 3,activity-dependent neuroprotector homeobox(ADNP),growth differentiation factor 11(GDF11),and regulator of G protein signalling 2 agree with m6A single nucleotide array results;ADNP and GDF11 m RNA expression decreased in DM-BMSCs.Furthermore,gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that most of these genes were enriched in metabolic processes.This study reveals the differential m6A sites of DM-BMSCs compared with N-BMSCs and identifies candidate target genes to enhance BMSC function and improve implantation success in T2DM patients.

关 键 词：PATIENTS IMPAIRED IMPLANTATION 

分 类 号：R587.1[医药卫生—内分泌] R783.6[医药卫生—内科学]