Disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss
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,...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-12-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-023-01122-w |
| _version_ | 1797363558738034688 |
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| author | Thanh-Tam Tran Gyuseok Lee Yun Hyun Huh Ki-Ho Chung Sun Young Lee Ka Hyon Park Seung Hee Kwon Min-Suk Kook Jang-Soo Chun Jeong-Tae Koh Je-Hwang Ryu |
| author_facet | Thanh-Tam Tran Gyuseok Lee Yun Hyun Huh Ki-Ho Chung Sun Young Lee Ka Hyon Park Seung Hee Kwon Min-Suk Kook Jang-Soo Chun Jeong-Tae Koh Je-Hwang Ryu |
| author_sort | Thanh-Tam Tran |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T16:23:00Z |
| format | Article |
| id | doaj.art-158a32c49f144c138b57ec12c0cfbf54 |
| institution | Directory Open Access Journal |
| issn | 2092-6413 |
| language | English |
| last_indexed | 2024-03-08T16:23:00Z |
| publishDate | 2023-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj.art-158a32c49f144c138b57ec12c0cfbf542024-01-07T12:12:48ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132023-12-0155122553256310.1038/s12276-023-01122-wDisruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone lossThanh-Tam Tran0Gyuseok Lee1Yun Hyun Huh2Ki-Ho Chung3Sun Young Lee4Ka Hyon Park5Seung Hee Kwon6Min-Suk Kook7Jang-Soo Chun8Jeong-Tae Koh9Je-Hwang Ryu10Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National UniversityDepartment of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National UniversitySchool of Life Sciences, Gwangju Institute of Science and TechnologyDepartment of Preventive and Public Health Dentistry, School of Dentistry, Chonnam National UniversityDepartment of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National UniversityDepartment of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National UniversityHard-tissue Biointerface Research Center, School of Dentistry, Chonnam National UniversityDepartment of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National UniversitySchool of Life Sciences, Gwangju Institute of Science and TechnologyDepartment of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National UniversityDepartment of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National UniversityAbstract 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.https://doi.org/10.1038/s12276-023-01122-w |
| spellingShingle | Thanh-Tam Tran Gyuseok Lee Yun Hyun Huh Ki-Ho Chung Sun Young Lee Ka Hyon Park Seung Hee Kwon Min-Suk Kook Jang-Soo Chun Jeong-Tae Koh Je-Hwang Ryu Disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss Experimental and Molecular Medicine |
| title | Disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss |
| title_full | Disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss |
| title_fullStr | Disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss |
| title_full_unstemmed | Disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss |
| title_short | Disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss |
| title_sort | disruption of cholesterol homeostasis triggers periodontal inflammation and alveolar bone loss |
| url | https://doi.org/10.1038/s12276-023-01122-w |
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