Sun Xuefei, Meng Xiujiao, Piao Yu, Dong Shaojie, Dong Qianqian
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.
Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Department of Endodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.
Int J Med Sci. 2024 Feb 4;21(4):664-673. doi: 10.7150/ijms.90485. eCollection 2024.
N6-Methyladenosine (mA) has been reported to play a dynamic role in osteoporosis and bone metabolism. However, whether mA is involved in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) remains unclear. Here, we found that methyltransferase-like 3 (METTL3) was up-regulated synchronously with mA during the osteogenic differentiation of hPDLSCs. Functionally, lentivirus-mediated knockdown of METTL3 in hPDLSCs impaired osteogenic potential. Mechanistic analysis further showed that METTL3 knockdown decreased mA methylation and reduced IGF2BP1-mediated stability of runt-related transcription factor 2 () mRNA, which in turn inhibited osteogenic differentiation. Therefore, METTL3-based mA modification favored osteogenic differentiation of hPDLSCs through IGF2BP1-mediated mRNA stability. Our study shed light on the critical roles of mA on regulation of osteogenic differentiation in hPDLSCs and served novel therapeutic approaches in vital periodontitis therapy.
据报道，N6-甲基腺苷（mA）在骨质疏松症和骨代谢中发挥着动态作用。然而，mA是否参与人牙周膜干细胞（hPDLSCs）的成骨分化仍不清楚。在此，我们发现，在hPDLSCs成骨分化过程中，类甲基转移酶3（METTL3）与mA同步上调。在功能上，慢病毒介导的hPDLSCs中METTL3基因敲低损害了成骨潜能。机制分析进一步表明，METTL3基因敲低降低了mA甲基化，并降低了IGF2BP1介导的 runt相关转录因子2（）mRNA稳定性，进而抑制了成骨分化。因此，基于METTL3的mA修饰通过IGF2BP1介导的mRNA稳定性促进了hPDLSCs的成骨分化。我们的研究揭示了mA在调控hPDLSCs成骨分化中的关键作用，并为重度牙周炎治疗提供了新的治疗方法。
