核糖体生物发生
成骨细胞
细胞生物学
牙周炎
Wnt信号通路
基因敲除
化学
线粒体生物发生
骨重建
癌症研究
生物
信号转导
医学
细胞凋亡
核糖体
核糖核酸
内科学
内分泌学
线粒体
基因
生物化学
体外
作者
Yiwen Zhang,Yiping Kong,Wenjie Zhang,Jinlin He,Zhanqi Zhang,Yanling Cai,Yiqing Zhao,Qiong Xu
标识
DOI:10.1186/s13148-024-01628-8
摘要
Abstract Background Periodontitis is a highly prevalent oral disease characterized by bacterium-induced periodontal inflammation and alveolar bone destruction. Osteoblast function is impaired in periodontitis with a global proteome change. METTL3 is the pivotal methyltransferase of N 6 -methyladenosine (m 6 A) that is recently proved to exert a crucial role in osteoblast differentiation. This study aims to investigate the role of METTL3 in osteoblast ribosome biogenesis in periodontitis progression. Results METTL3 was knocked down in osteoblasts, and the downregulated genes were enriched in ribosome and translation. METTL3 knockdown inhibited ribosome biogenesis and oxidative phosphorylation in LPS-stimulated osteoblasts, whereas METTL3 overexpression facilitated ribosomal and mitochondrial function. Mechanistically, METTL3 mediated osteoblast biological behaviors by activating Wnt/β-catenin/c-Myc signaling. METTL3 depletion enhanced the mRNA expression and stability of Dkk3 and Sostdc1 via YTHDF2. In periodontitis mice, METTL3 inhibitor SAH promoted alveolar bone loss and local inflammatory status, which were partially rescued by Wnt/β-catenin pathway activator CHIR-99021 HCl. Conclusions METTL3 promoted ribosome biogenesis and oxidative phosphorylation by activating Wnt/β-catenin/c-Myc signaling in LPS-treated osteoblasts and alleviated the inflammatory alveolar bone destruction in periodontitis mice.
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