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

作者全名："Qiao, Xin; Tang, Jie; Dou, Lei; Yang, Shiyao; Sun, Yuting; Mao, Hongchen; Yang, Deqin"

作者地址："[Qiao, Xin; Tang, Jie; Dou, Lei; Yang, Shiyao; Sun, Yuting; Mao, Hongchen; Yang, Deqin] Chongqing Med Univ, Stomatol Hosp, Dept Endodont, Chongqing 401147, Peoples R China; [Qiao, Xin; Tang, Jie; Dou, Lei; Mao, Hongchen; Yang, Deqin] Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Stomatol Hosp, Chongqing 401147, Peoples R China; [Qiao, Xin; Tang, Jie; Dou, Lei; Yang, Shiyao; Sun, Yuting; Mao, Hongchen] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing 401147, Peoples R China; [Yang, Shiyao; Sun, Yuting] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing 401147, Peoples R China; [Yang, Deqin] Chongqing Med Univ, Dept Endodont, Stomatol Hosp, 426 Songshi North Rd, Chongqing, Peoples R China"

通信作者："Yang, DQ (通讯作者)，Chongqing Med Univ, Dept Endodont, Stomatol Hosp, 426 Songshi North Rd, Chongqing, Peoples R China."

来源：INTERNATIONAL JOURNAL OF NANOMEDICINE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001052121400001

JCR分区：Q1

影响因子：6.6

年份：2023

卷号：18

期号：　

开始页：4683

结束页：4703

文献类型：Article

关键词：exosome; anti-inflammatory; osteogenesis; periodontitis; macrophages; IL-6; JAK2; STAT3 signaling pathway

摘要："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-1 & beta;, TNF-& alpha;and 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."

基金机构："National Natural Science Foundation of China [31970783, 32270888]; Program for Top talent Distinguished Professor from Chongqing Medical University [[2021] 215]; Program for Youth Innovation in Future Medicine from Chongqing Medical University [W0060]"

基金资助正文："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) ."