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Selenium Deficiency Can Promote the Expression of VEGF and Inflammatory Factors in Cartilage Differentiation and Mediates Cartilage Injury

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Abstract

Selenium plays a crucial role as a micronutrient, primarily exerting its biological functions through selenoproteins. It has been established that selenium deficiency adversely impacts cartilage development, leading to alterations in chondrocyte function. In regions with low selenium intake, endemic osteochondrosis has been documented, characterized by compromised growth plate and articular cartilage formation. Vascular endothelial growth factor (VEGF) stands out as a pivotal angiogenic factor, with elevated levels contributing significantly to vascular invasion into chondrocytes. This VEGF-mediated invasion serves as a key signal, prompting morphological changes in the growth plate and initiating cartilage remodeling. In animal models, the selenium deficiency group exhibited heightened levels of the cartilage damage marker matrix metalloproteinases 13 (MMP13). This resulted in articular cartilage degeneration, accompanied by a substantial increase in VEGF expression within the growth plate and articular cartilage, as compared to the normal group. In a chondrogenic progenitor cell (CPC) differentiation model, insufficient selenium induced chondrocyte damage and upregulated inflammatory factors such as inducible NO synthase (iNOS) and cyclooxygenase-2 (COX2). The selenium-deficient groups showed elevated expressions of VEGF, VEGFR2, MMP13, Collagen X, and Angiopoietin 1, accelerating the degradation of the extracellular matrix (ECM), which further promoted the development of cartilage-related diseases. Taken together, these findings provide novel insights for a better understanding of the role of low selenium in cartilage degeneration and angiogenesis. They shed light on the intricate influence of low selenium levels on the development of articular cartilage, emphasizing the interconnected pathways and processes involved.

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Data Availability

The data generated in this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank all individuals who participated in this work.

Funding

This study was supported by grants from the National Science Foundation of China (81672769).

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Author notes

  1. Xiang Meng and Xiumei Meng contributed equally to this work.

Authors and Affiliations

  1. Center for Rehabilitation Medicine, Department of Orthopedics, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China

    Xiang Meng, Zeju He, Ye Yuan, Yong Fan, Li Yin, Yu Tong, Zheping Hong, Senbo Zhu, Qiong Zhang & Qing Bi

  2. The First Affiliated Hospital of Wannan Medical University, Wuhu, Anhui, People’s Republic of China

    Xiumei Meng

  3. Center for Operating Room, Department of Nursing, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, China

    Qiong Zhang

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  1. Xiang Meng
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Contributions

Qing Bi and Qiong Zhang were responsible for supervision, validation, and funding acquisition. Xiang Meng was responsible for the verification experiment and writing—original draft preparation. Xiumei Meng was responsible for writing and editing. Ye Yuan, Zeju He, Yong Fan, Li Yin, Yu Tong, Zheping Hong, and Senbo Zhu contributed to the manuscript revision, searching the literature, and reading the submitted version. All authors contributed to the review and approved the submitted version.

Corresponding authors

Correspondence to Qiong Zhang or Qing Bi.

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Ethics Approval

This study was approved by the Medical Animal Research Ethics Committee of Zhejiang Provincial People’s Hospital (approval number: A2022060101).

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Meng, X., Meng, X., He, Z. et al. Selenium Deficiency Can Promote the Expression of VEGF and Inflammatory Factors in Cartilage Differentiation and Mediates Cartilage Injury. Biol Trace Elem Res (2023). https://doi.org/10.1007/s12011-023-04003-5

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