METTL3 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells through IGF2BP1-Mediated Regulation of Runx2 Stability. 2024

Xuefei Sun, and Xiujiao Meng, and Yu Piao, and Shaojie Dong, and Qianqian Dong
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, China.

N6-Methyladenosine (m6A) has been reported to play a dynamic role in osteoporosis and bone metabolism. However, whether m6A 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 m6A 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 m6A methylation and reduced IGF2BP1-mediated stability of runt-related transcription factor 2 (Runx2) mRNA, which in turn inhibited osteogenic differentiation. Therefore, METTL3-based m6A modification favored osteogenic differentiation of hPDLSCs through IGF2BP1-mediated Runx2 mRNA stability. Our study shed light on the critical roles of m6A on regulation of osteogenic differentiation in hPDLSCs and served novel therapeutic approaches in vital periodontitis therapy.

UI MeSH Term Description Entries
D008780 Methyltransferases A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1. Methyltransferase
D010012 Osteogenesis The process of bone formation. Histogenesis of bone including ossification. Bone Formation,Ossification, Physiologic,Endochondral Ossification,Ossification,Ossification, Physiological,Osteoclastogenesis,Physiologic Ossification,Endochondral Ossifications,Ossification, Endochondral,Ossifications,Ossifications, Endochondral,Osteoclastogeneses,Physiological Ossification
D010513 Periodontal Ligament The fibrous CONNECTIVE TISSUE surrounding the TOOTH ROOT, separating it from and attaching it to the alveolar bone (ALVEOLAR PROCESS). Alveolodental Ligament,Alveolodental Membrane,Gomphosis,Alveolodental Ligaments,Alveolodental Membranes,Gomphoses,Ligament, Alveolodental,Ligament, Periodontal,Membrane, Alveolodental,Periodontal Ligaments
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013234 Stem Cells Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells. Colony-Forming Units,Mother Cells,Progenitor Cells,Colony-Forming Unit,Cell, Mother,Cell, Progenitor,Cell, Stem,Cells, Mother,Cells, Progenitor,Cells, Stem,Colony Forming Unit,Colony Forming Units,Mother Cell,Progenitor Cell,Stem Cell
D050659 Core Binding Factor Alpha 1 Subunit A transcription factor that dimerizes with CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain and is involved in genetic regulation of skeletal development and CELL DIFFERENTIATION. AML3 Transcription Factor,Acute Myeloid Leukemia 3 Protein,CBFA-1 Protein,CBFA1 Protein,CBFalpha Runt Domain Transcription Factor 1,CBFalpha1 Protein,Osf2 Transcription Factor,PEBP2alphaA Protein,Runx2 Protein,SEF1 Protein,SL3-3 Enhancer Factor 1,CBFA 1 Protein,SL3 3 Enhancer Factor 1

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