Britanin alleviates chondrocyte ferroptosis in osteoarthritis by regulating the Nrf2-GPX4 axis

Chenwei Xiong; JingJing Shang; Zhentang Yu; Junjie Zhang; Kaisong Miao; Changlin Yu; Yong Huang; Yiping Weng; Xindie Zhou

Arabian Journal of Chemistry (Sep 2024)

Britanin alleviates chondrocyte ferroptosis in osteoarthritis by regulating the Nrf2-GPX4 axis

Chenwei Xiong,
JingJing Shang,
Zhentang Yu,
Junjie Zhang,
Kaisong Miao,
Changlin Yu,
Yong Huang,
Yiping Weng,
Xindie Zhou

Affiliations

Chenwei Xiong: Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China; Department of Orthopedics, Zhangjiajie People’s Hospital, Zhangjiajie 427000, China
JingJing Shang: Department of Pharmacy, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, China
Zhentang Yu: Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
Junjie Zhang: Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
Kaisong Miao: Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
Changlin Yu: Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China
Yong Huang: Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China; Corresponding author at: Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213000, China.
Yiping Weng: Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China; Corresponding author at: Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213000, China.
Xindie Zhou: Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213000, China; Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China; Corresponding author at: Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, 213000, China.

Journal volume & issue: Vol. 17, no. 9
p. 105918

Abstract

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Background: Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of the articular cartilage or inflamed joints. Britanin is a guaiacyl-type sesquiterpene lactone possessing anti-inflammatory and antioxidant activities. Methods: In this study, western blotting, Reverse-transcription PCR (RT-PCR), and immunofluorescent staining method were used to clarifying the molecular mechanisms of britanin in alleviating chondrocyte ferroptosis. The effect of britanin on reactive oxygen species (ROS) and lipid peroxidation levels in chondrocytes was examined by Dihydroethidium (DHE) stain and fluorescent dye BODIPY581 / 591 C11. The destabilized medial meniscus (DMM) model was used to mimic OA, then britanin was injected into the knee articular cavity. The morphological analysis was performed by hematoxylin and eosin (H&E) staining, Safranin O-Fast green staining and Micro-computed tomography (Micro-CT) analysis. Immunohistochemical analysis and Immunofluorescence assay was conducted to verify the effect of britanin in vivo. Results: The results revealed that britanin treatment regulates the expression of chondrocyte extracellular matrix–related factors, such as ADAMTS5, MMP13, SOX9, aggrecan, and COL2A1. Britanin also significantly reversed the influence of interleukin (IL)-1β on the levels of reactive oxygen species and lipid peroxidation and upregulated glutathione peroxidase 4 (GPX4) expression in IL-1β-induced chondrocytes. Erastin could alleviate the effects of britanin on chondrocytes. Moreover, britanin could prevent IL-1β-induced oxidative stress and ferroptosis in chondrocytes. Britanin also upregulated the expression of nuclear factor E2–related factor 2 (Nrf2) in IL-1β-induced chondrocytes, and Nrf2 activator played a similar role as that of britanin in IL-1β-induced chondrocytes. Furthermore, injecting britanin into the knee joints of OA rats alleviated cartilage destruction caused by surgical resection. Conclusions: These findings confirmed that britanin can inhibit ferroptosis in OA chondrocytes through the Nrf2-GPX4 pathway. Thus, britanin has the potential to be developed as a drug for OA therapy.

Published in Arabian Journal of Chemistry

ISSN: 1878-5352 (Print)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Chemistry
Website: http://www.journals.elsevier.com/arabian-journal-of-chemistry/

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