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

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.

Impact of dental pulp stromal cells-derived small extracellular vesicles on the properties and behavior of dental pulp stromal cells: An invitro-study

“…This agreed with Babaki et al [22] and Zhuang et al [23] who found cell proliferation enhancement in the cells treated with 0.2 mg/mL MTA and 50 µg/mL sEVs respectively. Using two different concentrations of sEVs showed that DPSC-sEVs promoted cell proliferation in a concentration-dependent manner which is in agreement with Qiao et al [39]. In our study, the combination group showed the greatest cell proliferation at the two different intervals in comparison with other groups indicating the addition of sEVs enhanced the MTA biocompatibility and cell proliferation ability.…”

The Cell Viability of Dental Materials by The Lactate Dehydrogenase Assay

“…In cell culture experiments, an experimental setup is prepared by keeping the cells of organisms in in vitro environments, in specifically manufactured containers, by controlling environmental conditions such as temperature and humidity, and by protecting them from contamination. Another advantage of cell culture studies is that cells taken from different kinds of living things, including humans, can be kept alive in a laboratory environment, cells taken from any tissue or organ can be used, and it eliminates many ethical concerns [14][15][16][17][18][19] . Different in vitro studies are carried out to determine whether dental materials have cytotoxic potential.…”

Mesenchymal stem cell-derived apoptotic bodies alleviate alveolar bone destruction by regulating osteoclast differentiation and function

“…During the apoptosis process, the chromatin block (nuclear fragments) formed by the condensation and fragmentation of nuclei and the membrane vesicles gradually divide into different sizes of vesicles, including exosomes, microvesicles and ABs. 33 , 34 Stem cell-derived exosomes increase the expression levels of osteogenic genes, regulate the polarization of macrophages and accelerate bone formation in defects of alveolar bone; 35 , 36 MSC-derived microvesicles showed a therapeutic potential for the treatment of clinical cartilage injury. 37 ABs are the major product of apoptotic cells and contain large amounts of regulatory molecules that are involved in a wide range of biological functions.…”