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Open AccessArticle
Hesperetin Attenuates T-2 Toxin-Induced Chondrocyte Injury by Inhibiting the p38 MAPK Signaling Pathway
by
Chunqing Lu
Chunqing Lu 1,2,†,
Wenjing Yang
Wenjing Yang 1,2,†,
Fang Chu
Fang Chu 1,2,
Sheng Wang
Sheng Wang 1,2,
Yi Ji
Yi Ji 2,3,
Zhipeng Liu
Zhipeng Liu 1,2,
Hao Yu
Hao Yu 1,2,
Shaoxiao Qin
Shaoxiao Qin 1,2,
Dianjun Sun
Dianjun Sun 1,2,
Zhe Jiao
Zhe Jiao 2,4,* and
Hongna Sun
Hongna Sun 1,2,*
1
Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, National Health Commission Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin 150081, China
2
Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health & Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Harbin Medical University, Harbin 150081, China
3
Institute of Keshan Disease, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
4
Institute for Kashin Beck Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Nutrients 2024, 16(18), 3107; https://doi.org/10.3390/nu16183107 (registering DOI)
Submission received: 7 July 2024
/
Revised: 1 September 2024
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Accepted: 12 September 2024
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Published: 14 September 2024
Abstract
Background: Hesperetin, a flavonoid derived from citrus fruits, exhibits potent antioxidant and anti-inflammatory activities and has been implicated in cartilage protection. However, its effectiveness against T-2 toxin-induced knee cartilage damage remains unclear. Methods: In this study, high-throughput sequencing analysis was employed to identify the key signaling pathways involved in T-2 toxin-induced articular cartilage damage in rats. Animal models were divided into the following groups: control, low-dose T-2 toxin, high-dose T-2 toxin, T-2 toxin + hesperetin, hesperetin, and vehicle. Pathological staining and immunohistochemistry were used to assess pathological changes, as well as the expression levels of the cartilage matrix-related proteins MMP13 and collagen II, along with the activation of the p38 MAPK signaling pathway. Additionally, primary rat chondrocytes were cultured to establish an in vitro model for investigating the underlying mechanism. Results: High-throughput sequencing analysis revealed the involvement of the MAPK signaling pathway in T-2 toxin-induced articular cartilage damage in rats. Hesperetin intervention in T-2 toxin-exposed rats attenuated pathological cartilage damage. Immunohistochemistry results demonstrated a significant reduction in collagen II protein expression in the high-dose T-2 toxin group (p < 0.01), accompanied by a significant increase in MMP13 protein expression (p < 0.01). In both the articular cartilage and the epiphyseal plate, the T-2 toxin + hesperetin group exhibited significantly higher collagen II protein expression than the high-dose T-2 toxin group (p < 0.05), along with significantly lower MMP13 protein expression (p < 0.05). Hesperetin inhibited the over-activation of the p38/MEF2C signaling axis induced by T-2 toxin in primary rat chondrocytes. Compared to the T-2 toxin group, the T-2 toxin + hesperetin group showed significantly reduced phosphorylation levels of p38 and protein expression levels of MEF2C (p < 0.001 or p < 0.05). Moreover, the T-2 toxin + hesperetin group exhibited a significant decrease in MMP13 protein expression (p < 0.05) and a significant increase in collagen II protein expression (p < 0.01) compared to the T-2 toxin group. Conclusions: T-2 toxin activates the p38 MAPK signaling pathway, causing knee cartilage damage in rats. Treatment with hesperetin inhibits the p38/MEF2C signaling axis, regulates collagen II and MMP13 protein expression, and reduces cartilage injury significantly.
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MDPI and ACS Style
Lu, C.; Yang, W.; Chu, F.; Wang, S.; Ji, Y.; Liu, Z.; Yu, H.; Qin, S.; Sun, D.; Jiao, Z.;
et al. Hesperetin Attenuates T-2 Toxin-Induced Chondrocyte Injury by Inhibiting the p38 MAPK Signaling Pathway. Nutrients 2024, 16, 3107.
https://doi.org/10.3390/nu16183107
AMA Style
Lu C, Yang W, Chu F, Wang S, Ji Y, Liu Z, Yu H, Qin S, Sun D, Jiao Z,
et al. Hesperetin Attenuates T-2 Toxin-Induced Chondrocyte Injury by Inhibiting the p38 MAPK Signaling Pathway. Nutrients. 2024; 16(18):3107.
https://doi.org/10.3390/nu16183107
Chicago/Turabian Style
Lu, Chunqing, Wenjing Yang, Fang Chu, Sheng Wang, Yi Ji, Zhipeng Liu, Hao Yu, Shaoxiao Qin, Dianjun Sun, Zhe Jiao,
and et al. 2024. "Hesperetin Attenuates T-2 Toxin-Induced Chondrocyte Injury by Inhibiting the p38 MAPK Signaling Pathway" Nutrients 16, no. 18: 3107.
https://doi.org/10.3390/nu16183107
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