Abstract
Temporomandibular joint osteoarthritis (TMJ OA) is a complex multifactorial disease that can be induced by inflammation and oxidative stress. Curcumin has been reported to have anti-inflammatory and antioxidant properties. Herein, the anti-inflammatory and antioxidant mechanisms of curcumin in TMJ OA were investigated. Curcumin treatment inhibited the expression of the inflammation mediators IL-6, iNOS, and COX-2 and of the matrix-degrading proteinases MMP-1, MMP-3, MMP-9, MMP-13, ADAMTS-4, and ADAMTS-5 and upregulated the mRNA levels of the cartilage anabolic factors COL2A1 and ACAN after IL-1β treatment. Curcumin treatment also decreased oxidative stress injury following IL-1β stimulation. Pathway analysis demonstrated that the ROS/Nrf2/HO-1-SOD2-NQO-1-GCLC signaling axis is a key axis through which curcumin activates the Nrf2/ARE pathway in TMJ inflammatory chondrocytes. Curcumin-induced anti-inflammatory and cartilage protective effects were significantly abrogated by specific Nrf2 siRNA. In vivo results demonstrated that curcumin treatment protected TMJ articular cartilage from progressive degradation. Our experimental results indicate that curcumin inhibits inflammation, oxidative stress, and the matrix degradation of TMJ inflammatory chondrocytes through the Nrf2/ARE signaling pathway, thereby exerting cartilage protective effects. This study provides insight into potential therapeutic approaches for TMJ OA.
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Abbreviations
- IL-1β:
-
Interleukin-1β
- IL-6:
-
Interleukin-6
- MMP:
-
Matrix metalloproteinase
- ADAMTS:
-
A disintegrin and metalloproteinase with thrombospondin motifs
- COX-2:
-
Cyclooxygenase-2
- iNOS:
-
Inducible nitric oxide synthase
- COL2A1:
-
Type 2 collagen
- ACAN:
-
Aggrecan
- GCLC:
-
Glutamate-cysteine ligase catalytic subunit
- ROS:
-
Reactive oxygen species
- Nrf2:
-
Nuclear factor (erythroid-derived 2)-Like 2
- NQO-1:
-
NAD(P)H: quinone oxidoreductase
- HO-1:
-
Heme oxygenase-1
- SOD2:
-
Superoxide dismutase 2
- ECM:
-
Extracellular matrix
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Funding
This work was supported by the National Natural Science Foundation of China (Grant No. 81800999), China Postdoctoral Science Foundation (Grant No. 2019 M653355), Scientific and Technological Research Program of Chongqing Municipal Education Commission (Grant No. KJQN201800414), and Program for Innovation Team Building at Institutions of Higher Education in Chongqing in 2016, Chongqing Medical Research Project (No. 2016MSXM046).
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The specific contributions of the authors are as follows:
(1) Study conception and design: Chao Jiang, Ping Luo, Xian Li, Ping Liu, Yong Li, Jie Xu.
(2) Data analysis and interpretation: Chao Jiang, Ping Luo, Xian Li, Ping Liu, Yong Li, Jie Xu.
(3) Data collection and management: Chao Jiang, Ping Luo.
(4) Drafting of the article: Chao Jiang, Ping Luo.
(5) Review of the article for important intellectual content and article revision: Xian Li, Ping Liu, Yong Li, Jie Xu.
(6) Final approval of the article: Chao Jiang, Ping Luo, Xian Li, Ping Liu, Yong Li, Jie Xu.
(7) Agreement to be accountable for all aspects of the work: Chao Jiang, Ping Luo, Xian Li, Ping Liu, Yong Li, Jie Xu.
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All animal experiments were performed according to the terms of the Animal Committee.
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The authors declare that they have no competing interests.
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Ethics approval for the collection of human TMJ cartilage samples was obtained from the Committee of Chongqing Medical University.
Ethical statement
The collection of human TMJ cartilage samples conformed to the Declaration of Helsinki.
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Jiang, C., Luo, P., Li, X. et al. Nrf2/ARE is a key pathway for curcumin-mediated protection of TMJ chondrocytes from oxidative stress and inflammation. Cell Stress and Chaperones 25, 395–406 (2020). https://doi.org/10.1007/s12192-020-01079-z
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DOI: https://doi.org/10.1007/s12192-020-01079-z