Restoration of Cementoblast Mineralization by Glutamine Under Inflammatory Conditions

INTRODUCTION AND AIMS: Cementoblasts are critical for cementum formation and periodontal regeneration during inflammatory diseases such as periodontitis and apical periodontitis (AP). Bacterial infection leads to metabolic changes in cementoblasts and reduces mineralization capability. This study aimed to fully elucidate the metabolic changes of cementoblasts in inflammatory mineralization and explore therapeutic strategies targeting metabolism. METHODS: Mouse cementoblasts cell line OCCM-30 were infected with Porphyromonas gingivalis (P.g) to model microbial infection stress. Metabolic profiling was performed using Seahorse assays and untargeted metabolomics. Genetic manipulation (knockdown/overexpression of Gls) and pharmacological inhibition (AMPK inhibitor Compound C) were used to dissect the mechanisms. An AP model was induced in C57BL/6 mice, and glutamine supplementation was administered to assess therapeutic effects in vivo. RESULTS: P.g infection suppressed glycolysis and oxidative phosphorylation but upregulated glutamine metabolism in cementoblasts. Knockdown of Gls inhibited mineralization by the cementoblasts, whereas glutamine supplementation or Gls overexpression restored mineralization ability. AMPK inhibition reduced GLS expression and mineralization by cementoblasts. In vivo, glutamine supplementation attenuated AP progression and cementum destruction. CONCLUSION: Glutamine supplementation compensates for energy deficits in inflamed cementoblasts via the AMPK/GLS signalling pathway. Targeting this pathway offers a potential therapeutic approach for cementum remineralization and periodontal regeneration. CLINICAL RELEVANCE: Glutamine supplementation restores mineralization by the cementoblasts under inflammatory conditions, which provides a novel theoretical foundation for the alleviation and treatment of periodontitis and apical periodontitis.