Serine Promotes Inflammatory Macrophage Polarisation in Periodontitis via NADSignalling.

Abstract

AIM: To investigate the role of serine in modulating macrophage polarisation and periodontal inflammation. MATERIALS AND METHODS: Saliva samples were obtained from periodontitis patients, healthy individuals and periodontitis remission patients for salivary metabolomics analysis. C57BL/6J mice were used to establish a ligature-induced periodontitis model. THP-1 cells were used in vitro to explore the mechanism underlying serine-mediated periodontitis. Micro-computed tomography, immunohistochemistry, quantitative real-time polymerase chain reaction, flow cytometry, western blotting, RNA sequencing and NAD/NADH detection were performed to explore the role of serine in periodontitis and the underlying mechanism. RESULTS: Salivary serine concentrations were significantly elevated in patients with periodontitis and correlated with disease severity. In vivo experiments showed that locally elevated serine concentrations exacerbated alveolar bone resorption in a mouse model of periodontitis. Transcriptomic analysis revealed that serine stimulation activated inflammation-related pathways, particularly the nicotinamide salvage pathway, which modulates NADlevels. Inhibition of intracellular serine transport using L-phenylglycine (L-phg) and mitochondrial complex I (MCI) activity using rotenone reduced inflammatory macrophage polarisation, decreased inflammatory markers and alleviated periodontal tissue damage. CONCLUSION: Serine-induced inflammatory macrophage polarisation, mediated through NADsignalling, plays a key role in periodontitis pathogenesis. Targeting serine transport and NADmetabolism may offer new therapeutic strategies for managing periodontitis.