Curcumin reverses erastin-induced chondrocyte ferroptosis by upregulating Nrf2
Osteoarthritis (OA) is associated with ferroptosis, a newly discovered form of programmed cell death associated with lipid peroxidation. Curcumin, the main monomer component in turmeric rhizomes, possesses antioxidant and anti-ferroptosis properties, but its effect on ferroptosis in chondrocytes of...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023073711 |
| _version_ | 1797646597150998528 |
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| author | Yizhao Zhou Zhen Jia Jing Wang Shu Huang Shu Yang Sheng Xiao Duo Xia Yi Zhou |
| author_facet | Yizhao Zhou Zhen Jia Jing Wang Shu Huang Shu Yang Sheng Xiao Duo Xia Yi Zhou |
| author_sort | Yizhao Zhou |
| collection | DOAJ |
| description | Osteoarthritis (OA) is associated with ferroptosis, a newly discovered form of programmed cell death associated with lipid peroxidation. Curcumin, the main monomer component in turmeric rhizomes, possesses antioxidant and anti-ferroptosis properties, but its effect on ferroptosis in chondrocytes of OA is unknown. This study aimed to investigate the protective effect and potential mechanism of curcumin on chondrocytes induced by erastin, a ferroptosis inducer. CCK-8 assays were used to assess cell viability in mouse primary chondrocytes treated with 3.33 μM erastin alone or in combination with different doses of curcumin. Various parameters were detected, including LDH, SOD, GSH-PX, MDA, ROS and Fe2+ contents. The ferroptosis-related proteins, such as SLC7A11, GPX4, TFR1, ACSL4, and FTH1, were examined using immunofluorescence and western blotting. Nrf2 was knocked down using siRNA to explore the molecular mechanism through which curcumin protects chondrocytes from erastin-induced ferroptosis. In a mouse model of knee ferroptosis induced by intracavity injection of 10 μL erastin (5 mg/mL), HE staining, Safranin O-Fast Green staining, and immunohistochemistry were employed to evaluate articular cartilage injury. The results demonstrated that erastin significantly suppressed the expression of SOD, GSH-PX, SLC7A11, GPX4, and FTH1 while upregulating the levels of LDH, MDA, ROS, ACSL4, and TFR1 in chondrocytes. Moreover, erastin-induced chondrocyte ferroptosis, lipid ROS, and Fe2+ production were reversed by curcumin. Additionally, curcumin significantly upregulated the expression level of the Nrf2 gene and protein. Silencing Nrf2 reversed the protective effect of curcumin on erastin-induced chondrocyte ferroptosis. In animal experiments, silencing Nrf2 counteracted the impact and damage of curcumin on erastin-induced ferroptosis of cartilage tissue in vivo, leading to significant inhibition of OA progression. Taken together, these findings suggest that curcumin can inhibit chondrocyte ferroptosis by activating the Nrf2 signaling pathway, providing further insight into the regulatory mechanism of curcumin in OA and supporting its potential therapeutic use in OA treatment. |
| first_indexed | 2024-03-11T15:03:59Z |
| format | Article |
| id | doaj.art-9344e910bd5440c3989ebc8694232712 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-11T15:03:59Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
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| series | Heliyon |
| spelling | doaj.art-9344e910bd5440c3989ebc86942327122023-10-30T06:05:26ZengElsevierHeliyon2405-84402023-10-01910e20163Curcumin reverses erastin-induced chondrocyte ferroptosis by upregulating Nrf2Yizhao Zhou0Zhen Jia1Jing Wang2Shu Huang3Shu Yang4Sheng Xiao5Duo Xia6Yi Zhou7Corresponding author.; Department of Orthopedics, Hunan Provincial People's Hospital, The First-Affiliated Hospital of Hunan Normal University, Changsha, 410005, ChinaDepartment of Orthopedics, Hunan Provincial People's Hospital, The First-Affiliated Hospital of Hunan Normal University, Changsha, 410005, ChinaDepartment of Orthopedics, Hunan Provincial People's Hospital, The First-Affiliated Hospital of Hunan Normal University, Changsha, 410005, ChinaDepartment of Orthopedics, Hunan Provincial People's Hospital, The First-Affiliated Hospital of Hunan Normal University, Changsha, 410005, ChinaDepartment of Orthopedics, Hunan Provincial People's Hospital, The First-Affiliated Hospital of Hunan Normal University, Changsha, 410005, ChinaDepartment of Orthopedics, Hunan Provincial People's Hospital, The First-Affiliated Hospital of Hunan Normal University, Changsha, 410005, ChinaDepartment of Orthopedics, Hunan Provincial People's Hospital, The First-Affiliated Hospital of Hunan Normal University, Changsha, 410005, ChinaCorresponding author.; Department of Orthopedics, Hunan Provincial People's Hospital, The First-Affiliated Hospital of Hunan Normal University, Changsha, 410005, ChinaOsteoarthritis (OA) is associated with ferroptosis, a newly discovered form of programmed cell death associated with lipid peroxidation. Curcumin, the main monomer component in turmeric rhizomes, possesses antioxidant and anti-ferroptosis properties, but its effect on ferroptosis in chondrocytes of OA is unknown. This study aimed to investigate the protective effect and potential mechanism of curcumin on chondrocytes induced by erastin, a ferroptosis inducer. CCK-8 assays were used to assess cell viability in mouse primary chondrocytes treated with 3.33 μM erastin alone or in combination with different doses of curcumin. Various parameters were detected, including LDH, SOD, GSH-PX, MDA, ROS and Fe2+ contents. The ferroptosis-related proteins, such as SLC7A11, GPX4, TFR1, ACSL4, and FTH1, were examined using immunofluorescence and western blotting. Nrf2 was knocked down using siRNA to explore the molecular mechanism through which curcumin protects chondrocytes from erastin-induced ferroptosis. In a mouse model of knee ferroptosis induced by intracavity injection of 10 μL erastin (5 mg/mL), HE staining, Safranin O-Fast Green staining, and immunohistochemistry were employed to evaluate articular cartilage injury. The results demonstrated that erastin significantly suppressed the expression of SOD, GSH-PX, SLC7A11, GPX4, and FTH1 while upregulating the levels of LDH, MDA, ROS, ACSL4, and TFR1 in chondrocytes. Moreover, erastin-induced chondrocyte ferroptosis, lipid ROS, and Fe2+ production were reversed by curcumin. Additionally, curcumin significantly upregulated the expression level of the Nrf2 gene and protein. Silencing Nrf2 reversed the protective effect of curcumin on erastin-induced chondrocyte ferroptosis. In animal experiments, silencing Nrf2 counteracted the impact and damage of curcumin on erastin-induced ferroptosis of cartilage tissue in vivo, leading to significant inhibition of OA progression. Taken together, these findings suggest that curcumin can inhibit chondrocyte ferroptosis by activating the Nrf2 signaling pathway, providing further insight into the regulatory mechanism of curcumin in OA and supporting its potential therapeutic use in OA treatment.http://www.sciencedirect.com/science/article/pii/S2405844023073711OsteoarthritisFerroptosisCurcuminNrf2Erastin |
| spellingShingle | Yizhao Zhou Zhen Jia Jing Wang Shu Huang Shu Yang Sheng Xiao Duo Xia Yi Zhou Curcumin reverses erastin-induced chondrocyte ferroptosis by upregulating Nrf2 Heliyon Osteoarthritis Ferroptosis Curcumin Nrf2 Erastin |
| title | Curcumin reverses erastin-induced chondrocyte ferroptosis by upregulating Nrf2 |
| title_full | Curcumin reverses erastin-induced chondrocyte ferroptosis by upregulating Nrf2 |
| title_fullStr | Curcumin reverses erastin-induced chondrocyte ferroptosis by upregulating Nrf2 |
| title_full_unstemmed | Curcumin reverses erastin-induced chondrocyte ferroptosis by upregulating Nrf2 |
| title_short | Curcumin reverses erastin-induced chondrocyte ferroptosis by upregulating Nrf2 |
| title_sort | curcumin reverses erastin induced chondrocyte ferroptosis by upregulating nrf2 |
| topic | Osteoarthritis Ferroptosis Curcumin Nrf2 Erastin |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023073711 |
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