Related Experiment Video
Updated: Jun 12, 2025
Induction of Periodontitis via a Combination of Ligature and Lipopolysaccharide Injection in a Rat Model
Published on: February 17, 2023
m6Am Methyltransferase PCIF1 Regulates Periodontal Inflammation
1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Abstract:
N6,2'-O-dimethyladenosine (m6Am), a common mRNA modification in eukaryotic capped mRNAs, plays a pivotal role in cellular functions and disease progression. However, its involvement in host inflammation remains elusive. Here, we demonstrate that loss of m6Am methyltransferase phosphorylated CTD interacting factor 1 (PCIF1) attenuates periodontal inflammation in whole-body and myeloid lineage-specific knockout mouse models. Pcif1 deletion inhibits macrophage phagocytosis and migration through m6Am-Csf1r signaling. In addition, colony-stimulating factor-1 receptor (CSF1R) is identified as a potential target for the treatment of periodontitis. We thus reveal a previously unrecognized role for PCIF1-mediated m6Am modification in governing macrophage responses and periodontal inflammation.
Insights
Loss of phosphorylated CTD interacting factor 1 (PCIF1) reduces periodontal inflammation by impacting macrophage function. This highlights PCIF1-mediated m6Am modification
Area of Science:
- Molecular Biology
- Immunology
- RNA Biology
Background:
- N6,2'-O-dimethyladenosine (m6Am) is a key mRNA modification in eukaryotes.
- The role of m6Am in host inflammation is not well understood.
- Periodontal inflammation is a significant health concern.
Purpose of the Study:
- To investigate the role of m6Am methyltransferase PCIF1 in periodontal inflammation.
- To elucidate the mechanisms by which PCIF1 influences macrophage function.
- To identify potential therapeutic targets for periodontitis.
Main Methods:
- Utilized whole-body and myeloid lineage-specific PCIF1 knockout mouse models.
- Assessed macrophage phagocytosis and migration.
- Analyzed m6Am-Csf1r signaling pathways.
Main Results:
- PCIF1 deficiency attenuated periodontal inflammation in knockout mice.
- Pcif1 deletion impaired macrophage phagocytosis and migration.
- m6Am-Csf1r signaling was identified as a key pathway affected by PCIF1 loss.
- CSF1R was identified as a potential therapeutic target.
Conclusions:
- PCIF1-mediated m6Am modification plays a critical role in regulating macrophage responses.
- Targeting PCIF1 or CSF1R may offer novel therapeutic strategies for periodontitis.
