Journal Article Research Support, Non-U.S. Gov't Epublish 5 citations
PubMed: 38267969 DOI: 10.1186/s13148-024-01628-8
METTL3 promotes osteoblast ribosome biogenesis and alleviates periodontitis.
Clin Epigenetics 16(1):18
Authors: Yiwen Zhang, Yiping Kong, Wenjie Zhang, Jinlin He, Zhanqi Zhang, Yongjie Cai, Yiqing Zhao, Qiong Xu
Affiliations
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Ling Yuan Xi Road, Guangzhou, 510055, China. Peking University Shenzhen Hospital, Shenzhen, 518036, China.
- Changsha Stomatological Hospital, Hunan University of Chinese Medicine, Changsha, 410004, China.
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Ling Yuan Xi Road, Guangzhou, 510055, China.
- Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Ling Yuan Xi Road, Guangzhou, 510055, China.
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-methyladenosine (mA) 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.
MeSH
Osteoblasts, Epigenesis, Genetic, Genes, Periodontitis, Ribosomes, Organelle Biogenesis
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