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Notch/NICD/RBP-J signaling axis regulates M1 polarization of macrophages mediated by advanced glycation end products

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Abstract

Advanced glycation end products (AGEs) aggregation and macrophages polarization are identified as the main factors contributing to bone diseases caused by aging or diabetes, such as senile or diabetic osteoporosis. Here, we aimed to elucidate the involvement and potential mechanism of AGEs in macrophages polarization and osteoclastogenesis. Firstly, AGEs-treated RAW264.7 macrophages were observed to up-regulate the release of nitric oxide (NO), the expression of M1-associated genes and the surface antigen marker CD86. The detection of osteoclast-related markers and TRAP staining revealed that the osteoclastogenic ability of M1 macrophages was markedly enhanced by AGEs. Further, AGEs were found to effectively activate the transduction of Notch signaling pathway and promote the nuclear translocation of NICD1. In addition, with the signals transduction of Notch pathway blocked by γ-secretase inhibitor DAPT and siRNA targeting silencing RBP-J, AGEs-induced M1 polarization was significantly mitigated. Collectively, we defined a critical role for AGEs in inducing M1 polarization and osteoclastogenesis of macrophages, and further identified Notch/NICD/RBP-J signaling axis as an essential mechanism regulating AGEs-mediated M1 polarization.

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Data availability statement

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by Program for the Natural Science Foundation of China (81470772) and the Medical Scientific Research Project of Chongqing (cstc2020jcyj-msxmX0307).

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Authors and Affiliations

  1. Stomatological Hospital of Chongqing Medical University, Chongqing, China

    Hao Tan, Wenjie Xu, Xiaoqian Ding, Huayu Ye, Yun Hu, Xinyi He, Ye Ming & Leilei Zheng

  2. Congqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China

    Hao Tan, Wenjie Xu, Xiaoqian Ding, Huayu Ye, Yun Hu, Xinyi He, Ye Ming & Leilei Zheng

  3. Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China

    Hao Tan, Wenjie Xu, Xiaoqian Ding, Huayu Ye, Yun Hu, Xinyi He, Ye Ming & Leilei Zheng

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  1. Hao Tan
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  2. Wenjie Xu
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  8. Leilei Zheng
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Hao Tan, Xiaoqian Ding, and Leilei Zheng. The first draft of the manuscript was written by Hao Tan and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Leilei Zheng.

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We declare that this study only used purchased murine cell lines and did not involve experimental animals or human participants, so no special ethical approval is required.

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Tan, H., Xu, W., Ding, X. et al. Notch/NICD/RBP-J signaling axis regulates M1 polarization of macrophages mediated by advanced glycation end products. Glycoconj J 39, 487–497 (2022). https://doi.org/10.1007/s10719-022-10062-y

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  • DOI: https://doi.org/10.1007/s10719-022-10062-y

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