{"title":"FTO通过TGFB2 m6A修饰的去甲基化促进人骨髓间充质干细胞成骨分化。","authors":"Xingyang Li, Wanyi Chen, Wenchao Zhong, Lecheng Tan, Kaitong Deng, Wei Cao, Mingjing Zhu, Antong Wu, Ziyi Zhang, Yuzhuo Hei, Siqing Jiang, Xin Li, Rui Li, Wenyi Cai, Janak L Pathak, Qingbin Zhang","doi":"10.1111/odi.15324","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To elucidate the role of m<sup>6</sup>A modification in the osteogenic differentiation of human BMSCs (hBMSCs) and the underlying mechanisms.</p><p><strong>Materials & methods: </strong>In this research, we analyzed the m<sup>6</sup>A modification and its impact on mRNA expression and osteogenic differentiation of hBMSCs. FTO was knocked down in hBMSCs using shRNAs, and the effect on osteogenic differentiation was evaluated. m<sup>6</sup>A-seq was performed to identify key m<sup>6</sup>A-methylation mRNAs during osteogenic differentiation. TGFB2 was knocked down to validate its role in FTO-regulated m<sup>6</sup>A-methylation-mediated osteogenesis.</p><p><strong>Results: </strong>We found downregulated global m<sup>6</sup>A modification in osteogenically differentiating hBMSCs. m<sup>6</sup>A eraser FTO expression was upregulated during the osteogenic differentiation of hBMSCs. FTO knockdown inhibited the osteogenic differentiation of hBMSCs. Downregulation of mRNA m<sup>6</sup>A modification was prominent in osteogenically differentiating hBMSCs. mRNA m<sup>6</sup>A modifications in osteogenically differentiating hBMSCs were mainly attributed to MAPK, focal adhesion, and TGFβ signaling. Finally, we revealed that FTO demethylates m<sup>6</sup>A abundance of TGFB2, promoting the TGFB2 expression in hBMSCs. Knockdown of TGFB2 inhibited the osteogenic differentiation of hBMSCs.</p><p><strong>Conclusion: </strong>These results indicate that upregulated m<sup>6</sup>A eraser FTO downregulates m<sup>6</sup>A modifications promoting TGFB2 expression in hBMSCs that trigger osteogenic differentiation, suggesting activation of FTO or TGFB2 as a strategy to promote hBMSC-based bone defect repair.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"FTO Promotes Osteogenic Differentiation of Human BMSCs via Demethylation of TGFB2 m<sup>6</sup>A Modifications.\",\"authors\":\"Xingyang Li, Wanyi Chen, Wenchao Zhong, Lecheng Tan, Kaitong Deng, Wei Cao, Mingjing Zhu, Antong Wu, Ziyi Zhang, Yuzhuo Hei, Siqing Jiang, Xin Li, Rui Li, Wenyi Cai, Janak L Pathak, Qingbin Zhang\",\"doi\":\"10.1111/odi.15324\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To elucidate the role of m<sup>6</sup>A modification in the osteogenic differentiation of human BMSCs (hBMSCs) and the underlying mechanisms.</p><p><strong>Materials & methods: </strong>In this research, we analyzed the m<sup>6</sup>A modification and its impact on mRNA expression and osteogenic differentiation of hBMSCs. FTO was knocked down in hBMSCs using shRNAs, and the effect on osteogenic differentiation was evaluated. m<sup>6</sup>A-seq was performed to identify key m<sup>6</sup>A-methylation mRNAs during osteogenic differentiation. TGFB2 was knocked down to validate its role in FTO-regulated m<sup>6</sup>A-methylation-mediated osteogenesis.</p><p><strong>Results: </strong>We found downregulated global m<sup>6</sup>A modification in osteogenically differentiating hBMSCs. m<sup>6</sup>A eraser FTO expression was upregulated during the osteogenic differentiation of hBMSCs. FTO knockdown inhibited the osteogenic differentiation of hBMSCs. Downregulation of mRNA m<sup>6</sup>A modification was prominent in osteogenically differentiating hBMSCs. mRNA m<sup>6</sup>A modifications in osteogenically differentiating hBMSCs were mainly attributed to MAPK, focal adhesion, and TGFβ signaling. Finally, we revealed that FTO demethylates m<sup>6</sup>A abundance of TGFB2, promoting the TGFB2 expression in hBMSCs. Knockdown of TGFB2 inhibited the osteogenic differentiation of hBMSCs.</p><p><strong>Conclusion: </strong>These results indicate that upregulated m<sup>6</sup>A eraser FTO downregulates m<sup>6</sup>A modifications promoting TGFB2 expression in hBMSCs that trigger osteogenic differentiation, suggesting activation of FTO or TGFB2 as a strategy to promote hBMSC-based bone defect repair.</p>\",\"PeriodicalId\":19615,\"journal\":{\"name\":\"Oral diseases\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-03-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oral diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/odi.15324\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oral diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/odi.15324","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
FTO Promotes Osteogenic Differentiation of Human BMSCs via Demethylation of TGFB2 m6A Modifications.
Objective: To elucidate the role of m6A modification in the osteogenic differentiation of human BMSCs (hBMSCs) and the underlying mechanisms.
Materials & methods: In this research, we analyzed the m6A modification and its impact on mRNA expression and osteogenic differentiation of hBMSCs. FTO was knocked down in hBMSCs using shRNAs, and the effect on osteogenic differentiation was evaluated. m6A-seq was performed to identify key m6A-methylation mRNAs during osteogenic differentiation. TGFB2 was knocked down to validate its role in FTO-regulated m6A-methylation-mediated osteogenesis.
Results: We found downregulated global m6A modification in osteogenically differentiating hBMSCs. m6A eraser FTO expression was upregulated during the osteogenic differentiation of hBMSCs. FTO knockdown inhibited the osteogenic differentiation of hBMSCs. Downregulation of mRNA m6A modification was prominent in osteogenically differentiating hBMSCs. mRNA m6A modifications in osteogenically differentiating hBMSCs were mainly attributed to MAPK, focal adhesion, and TGFβ signaling. Finally, we revealed that FTO demethylates m6A abundance of TGFB2, promoting the TGFB2 expression in hBMSCs. Knockdown of TGFB2 inhibited the osteogenic differentiation of hBMSCs.
Conclusion: These results indicate that upregulated m6A eraser FTO downregulates m6A modifications promoting TGFB2 expression in hBMSCs that trigger osteogenic differentiation, suggesting activation of FTO or TGFB2 as a strategy to promote hBMSC-based bone defect repair.
期刊介绍：
Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.
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