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ORIGINAL RESEARCH article

Front. Oral. Health
Sec. Oral Infections and Microbes
Volume 5 - 2024 | doi: 10.3389/froh.2024.1496819
This article is part of the Research Topic Modulation of Immune Response in Oral Health: Current Challenges and Future Directions View all articles

Blockade of connexin43-containing hemichannel attenuates the LPS-induced inflammatory response in human dental pulp cells by inhibiting the extracellular flux of ATP and HMGB1

Provisionally accepted
Ping Long Ping Long 1Peiling Hu Peiling Hu 1Ruotong Li Ruotong Li 1Xiaorong Lan Xiaorong Lan 1Yuanpei He Yuanpei He 1Shiting Li Shiting Li 1*Guangwen Li Guangwen Li 1,2
  • 1 School of Stomatology, Southwest Medical University, Lu Zhou, China
  • 2 Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, Sichuan, China, Lu Zhou, China

The final, formatted version of the article will be published soon.

    Introduction: Tissue repair can be promoted by moderate inflammation but suppressed by excessive levels. Therefore, control of excessive inflammation following removal of infection plays a critical role in promotion of pulpal repair. Connexin 43 (Cx43) forms hemichannels (HCs) or gap channels (GJs) to facilitate the delivery of small molecules between cells to regulate both inflammation and repair. Understanding the role of Cx43 in dental pulp may help develop a potential strategy to attenuate the inflammation and promote the formation of reparative dentin in deep caries. Methods: We firstly investigated the expression profile of Cx43 in infected human third molars by histological analysis; then, we detected channel activity of Cx43 and the effect of mediating release of small molecules in lipopolysaccharide (LPS)-induced inflammation in human dental pulp cells (hDPCs) by molecular biology methods. Results were analyzed by one-way ANOVA and the unpaired t-test. The level of significance was set at α=0.05. Results: Analysis showed that the expression of Cx43 was upregulated in human third molars as the degree of infection increased, and Cx43 was not only expressed in odontoblast layer, but also detected in cell-rich zone and pulp proper. LPS activated Cx43 HCs in hDPCs while inhibiting GJs; blockade of Cx43 HCs attenuated LPS-induced inflammation. Furthermore, LPS promoted the extracellular release of adenosine triphosphate (ATP) and high-mobility group box 1 (HMGB1) within hDPCs, thus exacerbating LPS-induced inflammation. The blockade of Cx43 HCs inhibited the extracellular release of ATP and HMGB1 within hDPCs. Conclusion: Collectively, our finding suggested that Cx43 plays a key role in infection and inflammation in dental pulp. LPS activates Cx43 HCs to mediate the extracellular release of ATP and HMGB1 to exacerbate LPS-induced inflammation of hDPCs.

    Keywords: deep caries, Connexin43 hemichannel, Inflammatory Response, Dental pulp cells, DAMPs

    Received: 22 Sep 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 Long, Hu, Li, Lan, He, Li and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Shiting Li, School of Stomatology, Southwest Medical University, Lu Zhou, China

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