Dental Pulp Stem Cell-Derived Exosomes Regulate Anti-Inflammatory and Osteogenesis in Periodontal Ligament Stem Cells and Promote the Repair of Experimental Periodontitis in Rats

Xin Qiao; Jie Tang; Lei Dou; Shiyao Yang; Yuting Sun; Hongchen Mao; Deqin Yang

doi:10.2147/IJN.S420967

Dental Pulp Stem Cell-Derived Exosomes Regulate Anti-Inflammatory and Osteogenesis in Periodontal Ligament Stem Cells and Promote the Repair of Experimental Periodontitis in Rats

Int J Nanomedicine. 2023 Aug 17:18:4683-4703. doi: 10.2147/IJN.S420967. eCollection 2023.

Authors

Xin Qiao^#^{1

2

3}, Jie Tang^#^{1

2

3}, Lei Dou^{1

2

3}, Shiyao Yang^{1

3

4}, Yuting Sun^{1

3

4}, Hongchen Mao^{1

2

3}, Deqin Yang^{1

2

3}

Affiliations

¹ Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, People's Republic of China.
² Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People's Republic of China.
³ Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, People's Republic of China.
⁴ Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, 401147, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: Dental pulp stem cell-derived exosomes (DPSC-EXO), which have biological characteristics similar to those of metrocytes, have been found to be closely associated with tissue regeneration. Periodontitis is an immune inflammation and tissue destructive disease caused by plaque, resulting in alveolar bone loss and periodontal epithelial destruction. It is not clear whether DPSC-EXO can be used as an effective therapy for periodontal regeneration. The purpose of this study was not only to verify the effect of DPSC-EXO on reducing periodontitis and promoting periodontal tissue regeneration, but also to reveal the possible mechanism.

Methods: DPSC-EXO was isolated by ultracentrifugation. Then it characterized by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) and Western Blot. In vitro, periodontal ligament stem cells (PDLSCs) were treated with DPSC-EXO, the abilities of cell proliferation, migration and osteogenic potential were evaluated. Furthermore, we detected the expression of IL-1β, TNF-αand key proteins in the IL-6/JAK2/STAT3 signaling pathway after simulating the inflammatory environment by LPS. In addition, the effect of DPSC-EXO on the polarization phenotype of macrophages was detected. In vivo, the experimental periodontitis in rats was established and treated with DPSC-EXO or PBS. After 4 weeks, the maxillae were collected and detected by micro-CT and histological staining.

Results: DPSC-EXO promoted the proliferation, migration and osteogenesis of PDLSCs in vitro. DPSC-EXO also regulated inflammation by inhibiting the IL-6/JAK2/STAT3 signaling pathway during acute inflammatory stress. In addition, the results showed that DPSC-EXO could polarize macrophages from the M1 phenotype to the M2 phenotype. In vivo, we found that DPSC-EXO could effectively reduce alveolar bone loss and promote the healing of the periodontal epithelium in rats with experimental periodontitis.

Conclusion: DPSC-EXO plays an important role in inhibiting periodontitis and promoting tissue regeneration. This study provides a promising acellular therapy for periodontitis.

Keywords: IL-6/JAK2/STAT3 signaling pathway; anti-inflammatory; exosome; macrophages; osteogenesis; periodontitis.

MeSH terms

Alveolar Bone Loss* / therapy
Animals
Anti-Inflammatory Agents
Dental Pulp
Exosomes*
Inflammation
Interleukin-6
Osteogenesis
Periodontal Ligament
Periodontitis* / therapy
Rats

Substances

Interleukin-6
Anti-Inflammatory Agents

Grants and funding

The reported work was supported in part by research grants from the Project Supported by the National Natural Science Foundation of China (No.31970783 to DY, NO.32270888 to DY), Program for Top talent Distinguished Professor from Chongqing Medical University to DY (NO.[2021]215), Program for Youth Innovation in Future Medicine from Chongqing Medical University (No. W0060 to DY).