Disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss

Oral diseases exhibit a significant association with metabolic syndrome, including dyslipidemia. However, direct evidence supporting this relationship is lacking, and the involvement of cholesterol metabolism in the pathogenesis of periodontitis (PD) has yet to be determined. In this study, we showed that high cholesterol caused periodontal inflammation in mice. Cholesterol homeostasis in human gingival fibroblasts was disrupted by enhanced uptake through C-X-C motif chemokine ligand 16 (CXCL16), upregulation of cholesterol hydroxylase (CH25H), and the production of 25-hydroxycholesterol (an oxysterol metabolite of CH25H). Retinoid-related orphan receptor α (RORα) mediated the transcriptional upregulation of inflammatory mediators; consequently, PD pathogenesis mechanisms, including alveolar bone loss, were stimulated. Our collective data provided direct evidence that hyperlipidemia is a risk factor for PD and supported that inhibition of the CXCL16-CH25H-RORα axis is a potential treatment mechanism for PD as a systemic disorder manifestation. Cholesterol disruption: the hidden trigger for periodontal inflammation Hypercholesterolemia, a type of hyperlipidemia, has been identified as a key factor in the development of periodontitis. This groundbreaking study by Tran et al. uncovers the complex mechanisms behind this association, revealing how an excess of cholesterol can trigger periodontal inflammation and alveolar bone loss. The researchers found that cholesterol dysregulation in periodontal cells, caused by increased CXCL16-mediated cholesterol influx and production of oxysterol metabolites by CH25H, stimulates the release of inflammatory mediators. This can lead to systemic diseases when released into the bloodstream. The study also highlighted the role of nuclear receptor RORα in mediating periodontitis pathogenesis triggered by cholesterol and its metabolites. These findings pave the way for new therapeutic approaches targeting individual molecular pathogenesis pathways in periodontitis treatment. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.