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Updated: Jun 19, 2026
Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
METTL14-Mediated m6A Modification of NEAT1_2 Releases YBX1 From Paraspeckles to Exacerbate Periodontitis
Juan Du1, Zi'ang Cheng1, Yu Zhang1
1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Aim:
To investigate the role and epigenetic mechanism of methyltransferase 14 (METTL14)-mediated N6-adenylate methylation (m6A) modification of long non-coding RNAs (lncRNAs) in the pathogenesis of periodontitis.
Materials And Methods:
A periodontal ligament-targeted Mettl14-cKO mouse model (Gli1-CreERT2;Mettl14fl/fl) was established using silk ligatures. Human periodontal ligament cells (PDLCs) were used for in vitro assays. MeRIP-seq, RNA-seq, RNA pull-down, mass spectrometry, RIP Co-IP and CUT&Tag were performed to elucidate the METTL14-NEAT1_2-YBX1 axis.
Results:
METTL14 expression was significantly up-regulated in inflamed periodontal tissue. METTL14 deficiency alleviated alveolar bone destruction and suppressed IL-6 expression in vivo and in vitro. Mechanistically, METTL14 catalysed m6A modification of nuclear paraspeckle assembly transcript 1_2 (NEAT1_2), facilitating NEAT1_2 degradation. NEAT1_2-organised paraspeckles (PSPs) sequestered the transcription factor Y-box binding protein 1 (YBX1) under normal conditions. In periodontitis, METTL14-induced NEAT1_2 down-regulation triggered PSP disassembly, resulting in the translocation of YBX1 to the nucleus and increased IL-6 transcription. Neat1_2 knockdown exacerbated bone loss and neutralised the protective effect of METTL14 deficiency.
Conclusion:
METTL14-mediated m6A modification exacerbates periodontitis by disrupting NEAT1_2-dependent PSP sequestration of YBX1. This study identifies the METTL14-NEAT1_2 axis as a critical regulator of periodontal inflammation, suggesting that METTL14 is a potential therapeutic target for periodontitis.
Insights
Methyltransferase 14 (METTL14) promotes periodontitis by modifying long non-coding RNAs (lncRNAs). This epigenetic mechanism involves the METTL14-NEAT1_2-YBX1 axis, highlighting METTL14 as a therapeutic target for periodontitis.
Area of Science:
- Epigenetics
- Molecular Biology
- Oral Biology
Background:
- Periodontitis is a prevalent inflammatory disease affecting tooth-supporting structures.
- The role of RNA modifications, specifically N6-adenylate methylation (m6A), in periodontitis pathogenesis is increasingly recognized.
- Long non-coding RNAs (lncRNAs) are implicated in various cellular processes, including inflammation.
Purpose of the Study:
- To investigate the role of methyltransferase 14 (METTL14) and its m6A modification of lncRNAs in periodontitis.
- To elucidate the underlying epigenetic mechanism involving the METTL14-NEAT1_2-YBX1 axis.
Main Methods:
- Established a Mettl14-conditional knockout (cKO) mouse model and utilized human periodontal ligament cells (PDLCs).
- Employed techniques including MeRIP-seq, RNA-seq, RNA pull-down, mass spectrometry, RIP Co-IP, and CUT&Tag.
- Investigated the interaction between METTL14, NEAT1_2, and YBX1 in the context of periodontitis.
Main Results:
- METTL14 expression was elevated in inflamed periodontal tissues, correlating with disease severity.
- METTL14 deficiency attenuated alveolar bone loss and reduced IL-6 expression in vivo and in vitro.
- METTL14-mediated m6A modification of NEAT1_2 led to its degradation, disrupting paraspeckle formation and promoting YBX1-mediated IL-6 transcription.
Conclusions:
- The METTL14-NEAT1_2 axis is a critical regulator of periodontal inflammation and bone destruction.
- METTL14 exacerbates periodontitis by impairing NEAT1_2-dependent sequestration of YBX1.
- Targeting METTL14 presents a potential therapeutic strategy for periodontitis.
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