Hyperhomocysteinaemia aggravates periodontitis by suppressing the Nrf2/HO-1 signalling pathway

Periodontitis, a common dental illness, causes periodontal tissue inflammation and irreversible bone loss, inevitably resulting in tooth loss. Hyperhomocysteinaemia (HHcy), defined as blood total homocysteine (Hcy) levels greater than 15 µmol/L, is linked to increased cardiovascular disease risk. Mo...

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Main Authors: Kaiqiang Yang, Yuting Yang, Ting Long, Xiaoxue Wang, Yeke Chen, Chenjiang He, Li Li, Xinbo Yang, Meixiu Jiang, Yichen Hu, Fang Dai, Li Song
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Redox Report
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Online Access:https://www.tandfonline.com/doi/10.1080/13510002.2025.2475691
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author Kaiqiang Yang
Yuting Yang
Ting Long
Xiaoxue Wang
Yeke Chen
Chenjiang He
Li Li
Xinbo Yang
Meixiu Jiang
Yichen Hu
Fang Dai
Li Song
author_facet Kaiqiang Yang
Yuting Yang
Ting Long
Xiaoxue Wang
Yeke Chen
Chenjiang He
Li Li
Xinbo Yang
Meixiu Jiang
Yichen Hu
Fang Dai
Li Song
author_sort Kaiqiang Yang
collection DOAJ
description Periodontitis, a common dental illness, causes periodontal tissue inflammation and irreversible bone loss, inevitably resulting in tooth loss. Hyperhomocysteinaemia (HHcy), defined as blood total homocysteine (Hcy) levels greater than 15 µmol/L, is linked to increased cardiovascular disease risk. Mounting evidence indicates a connection between HHcy and periodontitis; however, the underlying processes remain unknown. Herein, we explored the mechanisms by which HHcy exacerbates periodontal tissue inflammation and osteoclast formation. In an animal model of periodontitis treated with HHcy, periodontal attachment loss was aggravated, and both systemic and gingival tissue inflammation levels tended to increase; additionally, antioxidant-related proteins were suppressed and expressed at low levels, whereas oxidative damage-related protein expression increased. In RAW264.7 cells treated with LPS or LPS + Hcy, the LPS + Hcy group presented increased reactive oxygen species (ROS) fluorescence intensity, and Nrf2/HO-1 signalling pathway suppression was associated with inflammatory cytokine (TNF-α) expression. In monocyte osteoclasts treated with Rankl or Rankl + Hcy, the Rankl + Hcy group presented Nrf2/HO-1 signalling pathway suppression, an increase in osteoclast-related proteins (NFATc-1 and CTSK), and a more pronounced osteoclastic phenotype. Therefore, HHcy may exacerbate inflammation severity and osteoclast generation in periodontitis by promoting ROS production and inhibiting the Nrf2/HO-1 signalling pathway.
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spelling doaj-art-a55b7b6cf4854af8bb702e3870bd41f92025-08-20T02:30:12ZengTaylor & Francis GroupRedox Report1351-00021743-29282025-12-0130110.1080/13510002.2025.2475691Hyperhomocysteinaemia aggravates periodontitis by suppressing the Nrf2/HO-1 signalling pathwayKaiqiang Yang0Yuting Yang1Ting Long2Xiaoxue Wang3Yeke Chen4Chenjiang He5Li Li6Xinbo Yang7Meixiu Jiang8Yichen Hu9Fang Dai10Li Song11Center of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCenter of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCenter of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCenter of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCenter of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCenter of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCenter of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCenter of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaInstitute of Translational Medicine, Nanchang University, Nanchang, People’s Republic of ChinaCenter of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCenter of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCenter of Stomatology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaPeriodontitis, a common dental illness, causes periodontal tissue inflammation and irreversible bone loss, inevitably resulting in tooth loss. Hyperhomocysteinaemia (HHcy), defined as blood total homocysteine (Hcy) levels greater than 15 µmol/L, is linked to increased cardiovascular disease risk. Mounting evidence indicates a connection between HHcy and periodontitis; however, the underlying processes remain unknown. Herein, we explored the mechanisms by which HHcy exacerbates periodontal tissue inflammation and osteoclast formation. In an animal model of periodontitis treated with HHcy, periodontal attachment loss was aggravated, and both systemic and gingival tissue inflammation levels tended to increase; additionally, antioxidant-related proteins were suppressed and expressed at low levels, whereas oxidative damage-related protein expression increased. In RAW264.7 cells treated with LPS or LPS + Hcy, the LPS + Hcy group presented increased reactive oxygen species (ROS) fluorescence intensity, and Nrf2/HO-1 signalling pathway suppression was associated with inflammatory cytokine (TNF-α) expression. In monocyte osteoclasts treated with Rankl or Rankl + Hcy, the Rankl + Hcy group presented Nrf2/HO-1 signalling pathway suppression, an increase in osteoclast-related proteins (NFATc-1 and CTSK), and a more pronounced osteoclastic phenotype. Therefore, HHcy may exacerbate inflammation severity and osteoclast generation in periodontitis by promoting ROS production and inhibiting the Nrf2/HO-1 signalling pathway.https://www.tandfonline.com/doi/10.1080/13510002.2025.2475691Periodontitisoxidative stressROSNrf2bone lossinflammation
spellingShingle Kaiqiang Yang
Yuting Yang
Ting Long
Xiaoxue Wang
Yeke Chen
Chenjiang He
Li Li
Xinbo Yang
Meixiu Jiang
Yichen Hu
Fang Dai
Li Song
Hyperhomocysteinaemia aggravates periodontitis by suppressing the Nrf2/HO-1 signalling pathway
Redox Report
Periodontitis
oxidative stress
ROS
Nrf2
bone loss
inflammation
title Hyperhomocysteinaemia aggravates periodontitis by suppressing the Nrf2/HO-1 signalling pathway
title_full Hyperhomocysteinaemia aggravates periodontitis by suppressing the Nrf2/HO-1 signalling pathway
title_fullStr Hyperhomocysteinaemia aggravates periodontitis by suppressing the Nrf2/HO-1 signalling pathway
title_full_unstemmed Hyperhomocysteinaemia aggravates periodontitis by suppressing the Nrf2/HO-1 signalling pathway
title_short Hyperhomocysteinaemia aggravates periodontitis by suppressing the Nrf2/HO-1 signalling pathway
title_sort hyperhomocysteinaemia aggravates periodontitis by suppressing the nrf2 ho 1 signalling pathway
topic Periodontitis
oxidative stress
ROS
Nrf2
bone loss
inflammation
url https://www.tandfonline.com/doi/10.1080/13510002.2025.2475691
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