2. Academic Validation
  3. Bomidin attenuates inflammation of periodontal ligament stem cells and periodontitis in mice via inhibiting ferroptosis

Bomidin attenuates inflammation of periodontal ligament stem cells and periodontitis in mice via inhibiting ferroptosis

  • Int Immunopharmacol. 2023 Dec 22:127:111423. doi: 10.1016/j.intimp.2023.111423.
Wei Wu 1,  Guoqing Li 1,  Shuo Dong 1,  Catherine Huihan Chu 2,  Shanshan Ma 1,  Zhewei Zhang 1,  Shanshan Yuan 1,  Jin Wu 1,  Zixiang Guo 1,  Yue Shen 1,  Jiaohong Wang 1,  Chunbo Tang 3
Affiliations

Affiliations

  • 1 Department of Dental Implantology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing 210029, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China.
  • 2 Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China; Department of Orthodontic, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing 210029, China.
  • 3 Department of Dental Implantology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing 210029, China; Jiangsu Province Key Laboratory of Oral Diseases, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China. Electronic address: cbtang@njmu.edu.cn.
PMID: 38141410 DOI: 10.1016/j.intimp.2023.111423
Abstract

Aim: Periodontitis is a prevalent oral immunoinflammatory condition that is distinguished by the compromised functionality of periodontal ligament stem cells (PDLSCs). Bomidin, a new recombinant antimicrobial peptide (AMP), exhibits Antibacterial properties and modulates immune responses. Nevertheless, the precise anti-inflammatory impact of bomidin in periodontitis has yet to be fully elucidated. Thus, the study aimed to clarified the role of bomidin in modulating inflammation and its underlying mechanisms.

Methods: TNF-α was applied to treating PDLSCs for establishing a cell model of periodontitis. Bomidin, RSL3, ML385 and cycloheximide were also used to treat PDLSCs. Transcriptome Sequencing, RT-qPCR, western blot, immunofluorescence, immunohistochemistry, Fe2+ detection probe, molecular docking, Co-IP assay, ubiquitination assay and murine models of periodontitis were used.

Results: Our study demonstrated that bomidin effectively suppressed inflammation in PDLSCs stimulated by TNF-α, through down-regulating the MAPK and NF-κB signaling pathways. Furthermore, bomidin exerted inhibitory effects on Ferroptosis and activated the Keap1/Nrf2 pathway in the TNF-α group. There is a strong likelihood of bonding bomidin with Keap1 protein, which facilitated the degradation of Keap1 protein via the ubiquitin-proteasome pathway, leading to an enhanced translocation of Nrf2 protein to the nucleus.

Conclusions: Bomidin can directly bond to Keap1 protein, resulting in the degradation of Keap1 through the ubiquitin-proteasome pathway, thereby further activating the Keap1/Nrf2 pathway. The upregulation of the Keap1/Nrf2 signaling pathway was found to contribute to the suppression of Ferroptosis, ultimately alleviating inflammation in treatment of periodontitis.

Keywords

Bomidin; Ferroptosis; Keap1; Periodontitis; Ubiquitylation.

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