Disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss.
Thanh-Tam TranGyuseok LeeYun Hyun HuhKi-Ho ChungSun Young LeeKa Hyon ParkSeung Hee KwonMin-Suk KookJang-Soo ChunJeong Tae KohJe-Hwang RyuPublished in: Experimental & molecular medicine (2023)
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.
Keyphrases
- bone loss
- low density lipoprotein
- oxidative stress
- metabolic syndrome
- endothelial cells
- room temperature
- poor prognosis
- type diabetes
- cardiovascular disease
- high fat diet induced
- insulin resistance
- uric acid
- induced pluripotent stem cells
- electronic health record
- resting state
- functional connectivity
- climate change
- long non coding rna