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Remodeling periodontal osteoimmune microenvironment through MAPK/NFκB phosphorylation pathway of macrophage via intelligent ROS scavenging

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Abstract

Periodontitis is an inflammatory disorder which leads to the defect of tooth-supporting tissue, especially in alveolar bone. During this process, the polarization behavior of macrophages affects immune inflammation and bone regeneration in which reactive oxygen species (ROS) play an essential role. ROS level should be regulated to the physiological level to protect stem cells from the inflammatory immune microenvironment. Our previous study constructed a ROS-responsive nanoplatform (Pssl-NAC), which possessed ROS-responsive antioxidative effect and could be potentially applied in periodontitis. However, the connection among bone regeneration, inflammation and oxidative stress remained in osteoimmune regulation is not clear. To further investigate the mechanism of the way how Pssl-NAC works in the treatment of periodontitis would be meaningful. Here, we investigated the effect of PssL-NAC in the regulation of the osteoimmune microenvironment through macrophage polarization. Results show PssL-NAC regulated the macrophage polarization direction in an inflammatory environment by maintaining an appropriate level of intracellular ROS, in which the MAPK/NFκB phosphorylation pathway is particularly important. In the macrophage-human periodontal ligament stem cells (hPDLSCs) co-culture system, PssL-NAC treatment significantly enhanced the osteogenic differentiation of hPDLSCs. In vivo experiment further confirmed the M2-like macrophages increased in the periodontal tissue of rats, and the expression of iNOS and p65 decreased after PssL-NAC treatment. In conclusion, PssL-NAC regulates the osteoimmune microenvironment and protects stem cells from oxidative stress injury for bone regeneration, which provides a strategy for the treatment of periodontitis.

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The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

This study was supported by the Natural Science Foundation of Jiangsu Province under Grant [number BK20221177, BK20200665]; the “2015” Cultivation Program for Reserve Talents for Academic Leaders of Nanjing Stomatological School, Medical School of Nanjing University [number 0223A203, 0223A210]; Nanjing Clinical Research Center for Oral Diseases [number 2019060009]; and Key Project supported by Medical Science and Technology Development Foundation, Nanjing Department of Health under Grant [number ZKX22055, YKK20153].

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Author notes

  1. Xinyi Qiu and Haoran Peng contributed to this work equally.

Authors and Affiliations

  1. Department of Cariology and Endodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China

    Xinyi Qiu, Haoran Peng, Yue Zhao, Yijun Yu, Shuangshuang Ren & Leiying Miao

  2. Department of Periodontology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China

    Jie Yang

  3. Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China

    Chao Liu

  4. Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China

    Xinyi Qiu, Haoran Peng & Yue Zhao

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  1. Xinyi Qiu
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Correspondence to Chao Liu, Shuangshuang Ren or Leiying Miao.

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All procedures performed in this study were in accordance with the standards upheld by the Ethics Committee of Nanjing Stomatological Hospital, Affiliated Hospital of Medical School. All animal experiments were approved by the Ethics Committee of Nanjing Stomatological Hospital, Affiliated Hospital of Medical School for the use of animals and conducted in accordance with the National Institutes of Health Laboratory Animal Care and Use Guidelines (Approval No. NJSH-2022NL-009).

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Qiu, X., Peng, H., Zhao, Y. et al. Remodeling periodontal osteoimmune microenvironment through MAPK/NFκB phosphorylation pathway of macrophage via intelligent ROS scavenging. Human Cell 36, 1991–2005 (2023). https://doi.org/10.1007/s13577-023-00979-3

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