Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated <i>N</i><SUP>6</SUP>-methyladenosine modification of sclerostin

作者全名："Zhou, Jie; Zhu, Yanlin; Ai, Dongqing; Zhou, Mengjiao; Li, Han; Li, Guangyue; Zheng, Leilei; Song, Jinlin"

作者地址："[Zhou, Jie; Zhu, Yanlin; Ai, Dongqing; Zhou, Mengjiao; Li, Han; Li, Guangyue; Zheng, Leilei; Song, Jinlin] Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China; [Zhou, Jie; Zhu, Yanlin; Ai, Dongqing; Zhou, Mengjiao; Li, Han; Li, Guangyue; Zheng, Leilei; Song, Jinlin] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Zhou, Jie; Zhu, Yanlin; Ai, Dongqing; Zhou, Mengjiao; Li, Han; Li, Guangyue; Zheng, Leilei; Song, Jinlin] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China"

通信作者："Song, JL (通讯作者)，Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China.; Song, JL (通讯作者)，Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China.; Song, JL (通讯作者)，Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China."

来源：JOURNAL OF TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001098060600003

JCR分区：Q1

影响因子：6.1

年份：2023

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Diabetes mellitus; Periodontitis; Bone marrow mesenchymal stem cells; Osteogenesis; Advanced glycation end products; N-6-methyladenosine

摘要："Background Diabetes mellitus (DM) and periodontitis are two prevalent diseases with mutual influence. Accumulation of advanced glycation end products (AGEs) in hyperglycemia may impair cell function and worsen periodontal conditions. N-6-methyladenosine (m(6)A) is an important post-transcriptional modification in RNAs that regulates cell fate determinant and progression of diseases. However, whether m(6)A methylation participates in the process of periodontitis with diabetes is unclear. Thus, we aimed to investigate the effects of AGEs on bone marrow mesenchymal stem cells (BMSCs), elucidate the m(6)A modification mechanism in diabetes-associated periodontitis.Methods Periodontitis with diabetes were established by high-fat diet/streptozotocin injection and silk ligation. M(6)A modifications in alveolar bone were demonstrated by RNA immunoprecipitation sequence. BMSCs treated with AGEs, fat mass and obesity associated (FTO) protein knockdown and sclerostin (SOST) interference were evaluated by quantitative polymerase chain reaction, western blot, immunofluorescence, alkaline phosphatase and Alizarin red S staining.Results Diabetes damaged alveolar bone regeneration was validated in vivo. In vitro experiments showed AGEs inhibited BMSCs osteogenesis and influenced the FTO expression and m(6)A level in total RNA. FTO knockdown increased the m(6)A levels and reversed the AGE-induced inhibition of BMSCs differentiation. Mechanically, FTO regulated m(6)A modification on SOST transcripts, and AGEs affected the binding of FTO to SOST transcripts. FTO knockdown accelerated the degradation of SOST mRNA in presence of AGEs. Interference with SOST expression in AGE-treated BMSCs partially rescued the osteogenesis by activating Wnt Signaling.Conclusions AGEs impaired BMSCs osteogenesis by regulating SOST in an m(6)A-dependent manner, presenting a promising method for bone regeneration treatment of periodontitis with diabetes."

基金机构：Not applicable.

基金资助正文：Not applicable.