Resveratrol Alleviates Diabetic Periodontitis-Induced Alveolar Osteocyte Ferroptosis Possibly via Regulation of SLC7A11/GPX4
The mode and mechanism of diabetic periodontitis-induced alveolar-osteocyte death are still unclear. This study aimed to investigate the occurrence of ferroptosis in alveolar osteocytes during diabetic periodontitis and the therapeutic potential of resveratrol to alleviate osteocyte ferroptosis. Dia...
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MDPI AG
2023-04-01
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| author | Yue Li Zhijun Huang Shuaifei Pan Yuhui Feng Haokun He Shuguang Cheng Lijing Wang Liping Wang Janak Lal Pathak |
| author_facet | Yue Li Zhijun Huang Shuaifei Pan Yuhui Feng Haokun He Shuguang Cheng Lijing Wang Liping Wang Janak Lal Pathak |
| author_sort | Yue Li |
| collection | DOAJ |
| description | The mode and mechanism of diabetic periodontitis-induced alveolar-osteocyte death are still unclear. This study aimed to investigate the occurrence of ferroptosis in alveolar osteocytes during diabetic periodontitis and the therapeutic potential of resveratrol to alleviate osteocyte ferroptosis. Diabetic periodontitis was induced in C57/BL6-male mice and treated with or without resveratrol. Periodontitis pathogenicity was analyzed by micro-CT and histology, and alveolar-osteocyte ferroptosis was analyzed by immunohistochemistry. MLOY4 osteocytes were treated with <i>P. gingivalis</i>-derived lipopolysaccharide (LPS)+advanced glycosylated end products (AGEs) mimicking diabetic periodontitis condition in vitro, with or without resveratrol or ferrostatin-1 (ferroptosis inhibitor). Osteocyte ferroptosis and expression of inflammatory mediators were analyzed. Diabetic periodontitis aggravated periodontitis pathogenicity and inhibited the expression of GPX4 and SLC7A11 in alveolar osteocytes and resveratrol alleviated these effects. LPS+AGEs triggered osteocyte ferroptosis in vitro as indicated by the downregulated GPX4 and SLC7A11, upregulated malondialdehyde, disrupted mitochondrial morphology, and overexpressed pro-inflammatory mediators IL-1β, TNF-α, SOST, RANKL, and IL-6, and ferrostatin-1 or resveratrol treatment reversed these effects. LPS+AGEs upregulated pIKBα and pNF-κB p65 expression in osteocytes, and resveratrol or ferrostatin-1 reversed this effect. In conclusion, diabetic periodontitis triggers alveolar osteocyte ferroptosis possibly via disruption of the SLC7A11/GPX4 axis, and resveratrol has therapeutic potential to correct this biological event. |
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| spelling | doaj.art-54d11418f52f415b9c4fa97f1ce6824b2023-11-17T23:29:20ZengMDPI AGNutrients2072-66432023-04-01159211510.3390/nu15092115Resveratrol Alleviates Diabetic Periodontitis-Induced Alveolar Osteocyte Ferroptosis Possibly via Regulation of SLC7A11/GPX4Yue Li0Zhijun Huang1Shuaifei Pan2Yuhui Feng3Haokun He4Shuguang Cheng5Lijing Wang6Liping Wang7Janak Lal Pathak8Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, ChinaGuangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, ChinaGuangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, ChinaGuangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, ChinaGuangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, ChinaGuangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, ChinaGuangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, ChinaGuangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, ChinaGuangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, ChinaThe mode and mechanism of diabetic periodontitis-induced alveolar-osteocyte death are still unclear. This study aimed to investigate the occurrence of ferroptosis in alveolar osteocytes during diabetic periodontitis and the therapeutic potential of resveratrol to alleviate osteocyte ferroptosis. Diabetic periodontitis was induced in C57/BL6-male mice and treated with or without resveratrol. Periodontitis pathogenicity was analyzed by micro-CT and histology, and alveolar-osteocyte ferroptosis was analyzed by immunohistochemistry. MLOY4 osteocytes were treated with <i>P. gingivalis</i>-derived lipopolysaccharide (LPS)+advanced glycosylated end products (AGEs) mimicking diabetic periodontitis condition in vitro, with or without resveratrol or ferrostatin-1 (ferroptosis inhibitor). Osteocyte ferroptosis and expression of inflammatory mediators were analyzed. Diabetic periodontitis aggravated periodontitis pathogenicity and inhibited the expression of GPX4 and SLC7A11 in alveolar osteocytes and resveratrol alleviated these effects. LPS+AGEs triggered osteocyte ferroptosis in vitro as indicated by the downregulated GPX4 and SLC7A11, upregulated malondialdehyde, disrupted mitochondrial morphology, and overexpressed pro-inflammatory mediators IL-1β, TNF-α, SOST, RANKL, and IL-6, and ferrostatin-1 or resveratrol treatment reversed these effects. LPS+AGEs upregulated pIKBα and pNF-κB p65 expression in osteocytes, and resveratrol or ferrostatin-1 reversed this effect. In conclusion, diabetic periodontitis triggers alveolar osteocyte ferroptosis possibly via disruption of the SLC7A11/GPX4 axis, and resveratrol has therapeutic potential to correct this biological event.https://www.mdpi.com/2072-6643/15/9/2115diabetic periodontitisferroptosisresveratrolinflammatory mediatorsNF-κB signaling |
| spellingShingle | Yue Li Zhijun Huang Shuaifei Pan Yuhui Feng Haokun He Shuguang Cheng Lijing Wang Liping Wang Janak Lal Pathak Resveratrol Alleviates Diabetic Periodontitis-Induced Alveolar Osteocyte Ferroptosis Possibly via Regulation of SLC7A11/GPX4 Nutrients diabetic periodontitis ferroptosis resveratrol inflammatory mediators NF-κB signaling |
| title | Resveratrol Alleviates Diabetic Periodontitis-Induced Alveolar Osteocyte Ferroptosis Possibly via Regulation of SLC7A11/GPX4 |
| title_full | Resveratrol Alleviates Diabetic Periodontitis-Induced Alveolar Osteocyte Ferroptosis Possibly via Regulation of SLC7A11/GPX4 |
| title_fullStr | Resveratrol Alleviates Diabetic Periodontitis-Induced Alveolar Osteocyte Ferroptosis Possibly via Regulation of SLC7A11/GPX4 |
| title_full_unstemmed | Resveratrol Alleviates Diabetic Periodontitis-Induced Alveolar Osteocyte Ferroptosis Possibly via Regulation of SLC7A11/GPX4 |
| title_short | Resveratrol Alleviates Diabetic Periodontitis-Induced Alveolar Osteocyte Ferroptosis Possibly via Regulation of SLC7A11/GPX4 |
| title_sort | resveratrol alleviates diabetic periodontitis induced alveolar osteocyte ferroptosis possibly via regulation of slc7a11 gpx4 |
| topic | diabetic periodontitis ferroptosis resveratrol inflammatory mediators NF-κB signaling |
| url | https://www.mdpi.com/2072-6643/15/9/2115 |
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