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Purpose <p>This study aims to explore the interaction of Selenium (Se) deficiency and HT-2 toxin on cartilage homeostasis and the effect of Notch signaling pathway in this process.</p> Methods <p>Male C57BL/6 mice were randomly assigned to different dietary groups and subjected to either a Se-deficiency diet or a control diet for 4&#xa0;weeks, followed by exposure to varying doses of HT-2 toxin for 4&#xa0;weeks. Primary mouse chondrocytes were extracted and treated with DAPT (N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester), a γ-secretase inhibitor for the Notch signaling pathway, before combined intervention. Histological evaluation and transmission electron microscopy (TEM) were applied to assess cartilage damage, while immunohistochemical (IHC) analysis and Quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect extracellular matrix (ECM) metabolism and Notch signaling.</p> Results <p>HT-2 toxin, alone or in combination with Se deficiency, led to significant cartilage injury characterized by chondrocyte necrosis and ultrastructural abnormalities. IHC revealed increased expression of Adamts5 and decreased expression of Col2a1 and Acan in cartilage&#xa0;following exposure to HT-2 toxin, indicative of ECM degradation, which could be aggravated under Se deficiency. Additionally, activation of the Notch signaling pathway was observed in response to HT-2 toxin and Se deficiency, with upregulation of Notch pathway-related components. In vitro experiments further confirmed the role of the Notch pathway in ECM metabolism regulation, with partial protection against ECM depletion caused by HT-2 toxin and Se deficiency observed upon inhibition of the Notch pathway using DAPT.</p> Conclusion <p>This study demonstrate that Se deficiency exacerbates HT-2 toxin-induced cartilage degradation via Notch signaling activation, highlighting the interplay of environmental mycotoxins and nutritional deficits in KBD etiology and identify Notch signaling as a therapeutic target to mitigate disease progression.</p>

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Selenium deficiency exacerbates cartilage degradation caused by HT-2 toxin via notch signaling pathway activation

  • 期刊论文

  • 发表日期：

    2025年3月19日

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  • Peilin Meng,
  • Li Liu,
  • Ning Jiang,
  • Shuichu Hao,
  • Cong Yao,
  • Huan Liu,
  • Yingang Zhang,
  • Feng Zhang,
  • Yumeng Jia,
  • Xiong Guo

摘要

Purpose

This study aims to explore the interaction of Selenium (Se) deficiency and HT-2 toxin on cartilage homeostasis and the effect of Notch signaling pathway in this process.

Methods

Male C57BL/6 mice were randomly assigned to different dietary groups and subjected to either a Se-deficiency diet or a control diet for 4 weeks, followed by exposure to varying doses of HT-2 toxin for 4 weeks. Primary mouse chondrocytes were extracted and treated with DAPT (N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester), a γ-secretase inhibitor for the Notch signaling pathway, before combined intervention. Histological evaluation and transmission electron microscopy (TEM) were applied to assess cartilage damage, while immunohistochemical (IHC) analysis and Quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect extracellular matrix (ECM) metabolism and Notch signaling.

Results

HT-2 toxin, alone or in combination with Se deficiency, led to significant cartilage injury characterized by chondrocyte necrosis and ultrastructural abnormalities. IHC revealed increased expression of Adamts5 and decreased expression of Col2a1 and Acan in cartilage following exposure to HT-2 toxin, indicative of ECM degradation, which could be aggravated under Se deficiency. Additionally, activation of the Notch signaling pathway was observed in response to HT-2 toxin and Se deficiency, with upregulation of Notch pathway-related components. In vitro experiments further confirmed the role of the Notch pathway in ECM metabolism regulation, with partial protection against ECM depletion caused by HT-2 toxin and Se deficiency observed upon inhibition of the Notch pathway using DAPT.

Conclusion

This study demonstrate that Se deficiency exacerbates HT-2 toxin-induced cartilage degradation via Notch signaling activation, highlighting the interplay of environmental mycotoxins and nutritional deficits in KBD etiology and identify Notch signaling as a therapeutic target to mitigate disease progression.