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Serine Promotes Inflammatory Macrophage Polarisation in Periodontitis via NAD+ Signalling
Lingli Fang1,2,3, Jun Wang2, Jing Xiang4
1Dental Department, Clinical College, Chongqing Medical and Pharmaceutical College, Chongqing, China.
Journal of Clinical Periodontology
|November 2, 2025
Summary
Elevated serine levels worsen periodontitis by promoting inflammatory macrophage polarization via NAD+ signaling. Targeting serine transport and NAD+ metabolism may offer new therapeutic strategies for periodontitis.
Area of Science:
- Oral Biology
- Immunology
- Metabolism
Background:
- Periodontitis is a prevalent inflammatory disease affecting tooth-supporting structures.
- The role of specific amino acids, like serine, in periodontitis pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of serine in modulating macrophage polarization and periodontal inflammation.
- To elucidate the underlying molecular mechanisms linking serine to periodontitis.
Main Methods:
- Salivary metabolomics analysis in periodontitis patients and controls.
- In vivo periodontitis model in mice and in vitro studies using THP-1 cells.
- Molecular techniques including RNA sequencing, flow cytometry, and NAD+/NADH detection.
Main Results:
- Salivary serine levels correlated with periodontitis severity and exacerbated bone resorption in mice.
- Serine stimulation activated inflammation and the nicotinamide salvage pathway, impacting NAD+ levels.
- Inhibiting serine transport or mitochondrial complex I reduced inflammation and periodontal damage.
Conclusions:
- Serine drives periodontitis via inflammatory macrophage polarization mediated by NAD+ signaling.
- Targeting serine transport and NAD+ metabolism presents potential therapeutic avenues for periodontitis.
