Methyltransferase-like 3-mediated N6-methyladenosine modification of miR-7212-5p drives osteoblast differentiation and fracture healing |
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Authors: | Bobin Mi Yuan Xiong Chenchen Yan Lang Chen Hang Xue Adriana C. Panayi Liangcong Hu Yiqiang Hu Wu Zhou Faqi Cao Guohui Liu |
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Affiliation: | 1. Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;2. Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA |
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Abstract: | N6-methyladenosine (m6A) modification has been reported in various diseases and implicated in increasing numbers of biological processes. However, previous studies have not focused on the role of m6A modification in fracture healing. Here, we demonstrated that m6A modifications are decreased during fracture healing and that methyltransferase-like 3 (METTL3) is the main factor involved in the abnormal changes in m6A modifications. Down-regulation of METTL3 promotes osteogenic processes both in vitro and in vivo, and this effect is recapitulated by the suppression of miR-7212-5p maturation. Further studies have shown that miR-7212-5p inhibits osteoblast differentiation in MC3T3-E1 cells by targeting FGFR3. The present study demonstrated an important role of the METTL3/miR-7212-5p/FGFR3 axis and provided new insights on m6A modification in fracture healing. |
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Keywords: | fracture m6A METTL3 miRNA |
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