FTO/RUNX2 signaling axis promotes cementoblast differentiation under normal and inflammatory condition
FTO/RUNX2 signaling axis promotes cementoblast differentiation under normal and inflammatory condition
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DOI：
10.1016/j.bbamcr.2022.119358
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发表时间：
2022-09-08
影响因子：
5.1
通讯作者：
He，Hong
中科院分区：
文献类型：
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作者：
Sun，Qiao;Zhao，Tingting;He，Hong
N6-甲基腺苷（m6 A）是最常见的mRNA修饰，在各种生物学过程中起着至关重要的作用，但其在牙骨质形成中的作用在很大程度上仍然未知。在这里，使用时间序列转录组学分析，我们揭示了mRNA m6 A去甲基化酶脂肪质量和肥胖相关蛋白（FTO）参与牙骨质形成。在OCCM-30细胞模型和鼠异位骨形成模型中，敲低FTO降低成牙骨质细胞分化和矿化。从机制上讲，我们发现FTO直接结合Runt相关转录因子2（Runx 2）mRNA，这是一种重要的牙骨质形成因子，从而在成牙骨质细胞分化时保护其免受含有YTH结构域的家族蛋白2（YTHDF 2）介导的降解。敲低YTHDF 2可恢复FTO敲低细胞中Runx 2的表达。在炎症条件下，TNF-α可部分通过FTO/RUNX 2轴抑制成牙骨质细胞的分化和矿化。总之，我们的研究揭示了FTO/RUNX 2轴在正常和病理性牙骨质形成中的重要调节作用。
N6-methyladenosine (m6A) is the most prevalent mRNA modification which plays crucial roles in various biological processes, but its role in cementogenesis remains largely unknown. Here, using time-series transcriptomic analysis, we reveal that mRNA m6A demethylase Fat mass and obesity-associated protein (FTO) is involved in cementogenesis. Knocking down FTO decreases cementoblast differentiation and mineralization in both OCCM-30 cellular model and murine ectopic bone formation model. Mechanistically, we find that FTO directly binds Runt-related transcription factor 2 (Runx2) mRNA, an important cementogenesis factor, thus protecting it from YTH domain-containing family protein 2 (YTHDF2) mediated degradation, when cementoblasts are differentiating. Knocking down YTHDF2 restores the expression ofRunx2in FTO-knockdown cells. Moreover, under inflammatory conditions, TNF-α inhibits cementoblast differentiation and mineralization partly through FTO/RUNX2 axis. Collectively, our study reveals an important regulatory role of FTO/RUNX2 axis in normal and pathological cementogenesis.