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Exp. Mol. Med., Dec 01 2023, | https://doi.org/10.1038/s12276-023-01122-w Disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss

Thanh-Tam Tran^1,2, Gyuseok Lee^1,2, Yun Hyun Huh³, Ki-Ho Chung⁴, Sun Young Lee¹, Ka Hyon Park¹, Seung Hee Kwon², Min-Suk Kook⁵, Jang-Soo Chun³, Jeong-Tae Koh^1,2 and Je-Hwang Ryu^1,2

¹Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Korea.

²Hard-tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju, Korea.

³School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.

⁴Department of Preventive and Public Health Dentistry, School of Dentistry, Chonnam National University, Gwangju, Korea.

⁵Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University, Gwangju, Korea.

Corresponding author : Correspondence to Je-Hwang Ryu.

Abstract

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.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2023-12-04)
연구진국내 연구진
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