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Updated: May 21, 2025
Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Selenium deficiency exacerbates cartilage degradation caused by HT-2 toxin via notch signaling pathway activation
Peilin Meng1,2,3, Li Liu2,3, Ning Jiang2,3
1Northwest Women's and Children's Hospital, Xi'an, 710061, People's Republic of China.
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.
Insights
Selenium deficiency worsens HT-2 toxin-induced cartilage damage by activating Notch signaling. This highlights how mycotoxins and nutrient deficits impact KBD and suggests Notch signaling as a therapeutic target.
Area of Science:
- Biochemistry
- Toxicology
- Cell Biology
Background:
- Cartilage homeostasis is crucial for joint function.
- Environmental mycotoxins and nutritional status can impact cartilage health.
- The role of Selenium (Se) deficiency and HT-2 toxin in cartilage degradation requires further investigation.
Purpose of the Study:
- To explore the interaction between Selenium (Se) deficiency and HT-2 toxin on cartilage homeostasis.
- To investigate the involvement of the Notch signaling pathway in this process.
- To identify potential therapeutic targets for mitigating cartilage degradation.
Main Methods:
- Male C57BL/6 mice were fed Se-deficient or control diets and exposed to HT-2 toxin.
- Primary mouse chondrocytes were treated with DAPT, a Notch signaling inhibitor.
- Histological evaluation, TEM, IHC, and qRT-PCR were used to assess cartilage damage and ECM metabolism.
Main Results:
- HT-2 toxin and Se deficiency caused significant cartilage injury, chondrocyte necrosis, and ECM degradation.
- Notch signaling pathway components were upregulated in response to HT-2 toxin and Se deficiency.
- Inhibition of Notch signaling partially protected against ECM depletion in vitro.
Conclusions:
- Se deficiency exacerbates HT-2 toxin-induced cartilage degradation through Notch signaling activation.
- This study reveals the interplay of mycotoxins and nutritional deficits in KBD etiology.
- Notch signaling is identified as a potential therapeutic target for KBD progression.
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