Methyltransferase-like 3-mediated N6-methyladenosine modification of miR-7212-5p drives osteoblast differentiation and fracture healing
Methyltransferase-like 3-mediated N6-methyladenosine modification of miR-7212-5p drives osteoblast differentiation and fracture healing
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DOI：
10.1111/jcmm.15284
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发表时间：
2020-04-19
影响因子：
5.3
通讯作者：
Liu, Guohui
中科院分区：
文献类型：
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作者：
Mi, Bobin;Xiong, Yuan;Liu, Guohui
N6-甲基腺苷（m6 A）修饰已被报道在各种疾病中，并涉及越来越多的生物过程。然而，以前的研究并没有集中在m6 A修饰在骨折愈合中的作用。在这里，我们证明了m6 A修饰在骨折愈合过程中减少，并且甲基转移酶样3（methyltransferase-like 3，缩写为L3）是参与m6 A修饰异常变化的主要因素。在体外和体内，胃L3的下调促进成骨过程，并且这种作用通过抑制miR-7212- 5 p成熟而重现。进一步的研究表明，miR-7212- 5 p通过靶向FGFR 3抑制MC 3 T3-E1细胞中的成骨细胞分化。本研究证明了胃L3/miR-7212- 5 p/FGFR 3轴的重要作用，并提供了关于m6 A修饰在骨折愈合中的新见解。
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.