2. Academic Validation
  3. Crosstalk between reactive oxygen species and Dynamin-related protein 1 in periodontitis

Crosstalk between reactive oxygen species and Dynamin-related protein 1 in periodontitis

  • Free Radic Biol Med. 2021 Aug 20;172:19-32. doi: 10.1016/j.freeradbiomed.2021.05.031.
Lixi Shi 1,  Yinghui Ji 2,  Shufan Zhao 3,  Houxuan Li 4,  Yun Jiang 2,  Jiajie Mao 2,  Yang Chen 2,  Xiaorong Zhang 5,  Yixin Mao 2,  Xiaoyu Sun 6,  Panpan Wang 7,  Jianfeng Ma 8,  Shengbin Huang 9
Affiliations

Affiliations

  • 1 Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Shantou Centre Hospital, Shantou, China.
  • 2 Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
  • 3 Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Department of Oral Maxillofacial Surgery, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
  • 4 Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China; Department of Periodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
  • 5 Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Department of Endodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
  • 6 Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Department of Periodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
  • 7 South China Center of Craniofacial Stem Cell Research, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, China; Department of Periodontology, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.
  • 8 Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China. Electronic address: dentistmacn@aliyun.com.
  • 9 Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China. Electronic address: huangsb003@wmu.edu.cn.
PMID: 34052344 DOI: 10.1016/j.freeradbiomed.2021.05.031
Abstract

Excessive generation of Reactive Oxygen Species (ROS) have great impacts on the development of periodontitis. Dynamin-related protein 1 (Drp1) mediated mitochondrial fission is the main reason and the result of excessive ROS generation. However, whether Drp1 and crosstalk between ROS and Drp1 contribute to the process of periodontitis remains elusive. We herein investigated the role and functional significance of crosstalk between ROS and Drp1 in periodontitis. Firstly, human periodontal ligament cells (hPDLCs) were treated with hydrogen peroxide (H2O2) and ROS inhibitor N-acetyl-cysteine (NAC) or Drp1 inhibitor mitochondrial division inhibitor 1 (Mdivi-1). Cell viability, Apoptosis, osteogenic differentiation, expression of Drp1, and mitochondrial function were investigated. Secondly, mice with periodontitis were treated with NAC or Mdivi-1. Finally, gingival tissues were collected from periodontitis patients and healthy individuals to evaluate ROS and Drp1 levels. H2O2 induced cellular injury and inflammation, excessive ROS production, mitochondrial abnormalities, and increased expression of p-Drp1 and Drp1 in hPDLCs, which could be reversed by NAC and Mdivi-1. Moreover, both NAC and Mdivi-1 ameliorated tissue damage and inflammation, and decreased expression of p-Drp1 and Drp1 in mice with periodontitis. More importantly, patients with periodontitis presented significantly higher levels of ROS-induced oxidative damage and p-Drp1 than that in healthy individuals and correlated with clinical parameters. In summary, ROS-Drp1 crosstalk greatly promotes the development of periodontitis. Pharmacological blockade of this crosstalk might be a novel therapeutic strategy for periodontitis.

Keywords

Drp1; Inflammation; Mitochondrial dysfunction; Periodontitis; ROS; Tissue damage.

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