Calcitriol-enhanced autophagy in gingival epithelium attenuates periodontal inflammation in rats with type 2 diabetes mellitus
Type 2 diabetes mellitus (T2DM)-associated periodontitis is a common disease with high prevalence, associated with persistent infection and complicated manifestations. Calcitriol (1 alpha, 25-dihydroxyvitamin D3, 1,25D) is the active form of vitamin D that plays a protective role in immune regulatio...
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| Format: | Article |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.1051374/full |
| _version_ | 1797956372621426688 |
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| author | Yanan Wang Maoting Huang Wanlin Xu Fulong Li Chunliang Ma Xiaolin Tang |
| author_facet | Yanan Wang Maoting Huang Wanlin Xu Fulong Li Chunliang Ma Xiaolin Tang |
| author_sort | Yanan Wang |
| collection | DOAJ |
| description | Type 2 diabetes mellitus (T2DM)-associated periodontitis is a common disease with high prevalence, associated with persistent infection and complicated manifestations. Calcitriol (1 alpha, 25-dihydroxyvitamin D3, 1,25D) is the active form of vitamin D that plays a protective role in immune regulation, bone metabolism, and inflammatory response. In this study, we constructed a T2DM model in rats by combining a high-fat diet with low-dose streptozotocin. The periodontitis model in rats was developed by ligation and Porphyromonas gingivalis (ATCC 33277) inoculation. Rats were randomly divided into five groups: non-diabetic blank, diabetic blank, diabetes with calcitriol treatment, diabetes with 3-methyladenine (3-MA) treatment, or diabetes with calcitriol and 3-MA treatment. The diabetic rats exhibited an intense inflammatory response and decreased autophagy compared with the non-diabetic rats. Intraperitoneal injection of calcitriol and autophagy inhibitor (3-MA) allowed us to explore the effect of calcitriol on inflammation in the gingival epithelium and the role of autophagy in this process. Treatment with calcitriol resulted in the decreased expression of NFκB-p65, p62/SQSTM1 and inflammatory response and increased expression of LC3-II/LC3-I. Application of 3-MA significantly suppressed autophagy, which was apparently retrieved by calcitriol. Antibacterial peptide (LL-37) is the only antimicrobial peptide in the cathelicidin family that is found in the human body, and it exhibits a broad spectrum of antibacterial activity and regulates the immune system. In the present study, our findings indicated that calcitriol-enhanced autophagy may attenuated periodontitis and the decrease of LL-37 was rescued by calcitriol treatment in the gingival epithelial cells of T2DM rats. Our study provides evidence for the application of calcitriol as an adjunctive treatment for T2DM-associated periodontitis. |
| first_indexed | 2024-04-10T23:47:59Z |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T23:47:59Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-55053e028c18471e81675d7a920669b82023-01-10T22:01:36ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-01-011310.3389/fendo.2022.10513741051374Calcitriol-enhanced autophagy in gingival epithelium attenuates periodontal inflammation in rats with type 2 diabetes mellitusYanan WangMaoting HuangWanlin XuFulong LiChunliang MaXiaolin TangType 2 diabetes mellitus (T2DM)-associated periodontitis is a common disease with high prevalence, associated with persistent infection and complicated manifestations. Calcitriol (1 alpha, 25-dihydroxyvitamin D3, 1,25D) is the active form of vitamin D that plays a protective role in immune regulation, bone metabolism, and inflammatory response. In this study, we constructed a T2DM model in rats by combining a high-fat diet with low-dose streptozotocin. The periodontitis model in rats was developed by ligation and Porphyromonas gingivalis (ATCC 33277) inoculation. Rats were randomly divided into five groups: non-diabetic blank, diabetic blank, diabetes with calcitriol treatment, diabetes with 3-methyladenine (3-MA) treatment, or diabetes with calcitriol and 3-MA treatment. The diabetic rats exhibited an intense inflammatory response and decreased autophagy compared with the non-diabetic rats. Intraperitoneal injection of calcitriol and autophagy inhibitor (3-MA) allowed us to explore the effect of calcitriol on inflammation in the gingival epithelium and the role of autophagy in this process. Treatment with calcitriol resulted in the decreased expression of NFκB-p65, p62/SQSTM1 and inflammatory response and increased expression of LC3-II/LC3-I. Application of 3-MA significantly suppressed autophagy, which was apparently retrieved by calcitriol. Antibacterial peptide (LL-37) is the only antimicrobial peptide in the cathelicidin family that is found in the human body, and it exhibits a broad spectrum of antibacterial activity and regulates the immune system. In the present study, our findings indicated that calcitriol-enhanced autophagy may attenuated periodontitis and the decrease of LL-37 was rescued by calcitriol treatment in the gingival epithelial cells of T2DM rats. Our study provides evidence for the application of calcitriol as an adjunctive treatment for T2DM-associated periodontitis.https://www.frontiersin.org/articles/10.3389/fendo.2022.1051374/fulltype 2 diabetes mellitusPorphyromonas gingivaliscalcitriolLL-37autophagyrats model |
| spellingShingle | Yanan Wang Maoting Huang Wanlin Xu Fulong Li Chunliang Ma Xiaolin Tang Calcitriol-enhanced autophagy in gingival epithelium attenuates periodontal inflammation in rats with type 2 diabetes mellitus Frontiers in Endocrinology type 2 diabetes mellitus Porphyromonas gingivalis calcitriol LL-37 autophagy rats model |
| title | Calcitriol-enhanced autophagy in gingival epithelium attenuates periodontal inflammation in rats with type 2 diabetes mellitus |
| title_full | Calcitriol-enhanced autophagy in gingival epithelium attenuates periodontal inflammation in rats with type 2 diabetes mellitus |
| title_fullStr | Calcitriol-enhanced autophagy in gingival epithelium attenuates periodontal inflammation in rats with type 2 diabetes mellitus |
| title_full_unstemmed | Calcitriol-enhanced autophagy in gingival epithelium attenuates periodontal inflammation in rats with type 2 diabetes mellitus |
| title_short | Calcitriol-enhanced autophagy in gingival epithelium attenuates periodontal inflammation in rats with type 2 diabetes mellitus |
| title_sort | calcitriol enhanced autophagy in gingival epithelium attenuates periodontal inflammation in rats with type 2 diabetes mellitus |
| topic | type 2 diabetes mellitus Porphyromonas gingivalis calcitriol LL-37 autophagy rats model |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.1051374/full |
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