Effects of periodontal ligament stem cell‐derived exosomes on osteoblastic proliferation, migration, differentiation, apoptosis, and signaling pathways

Abstract

ObjectivePeriodontitis is characterized by alveolar bone injury and absorption, with high incidence and poor treatment effect. Proliferation, migration, differentiation and apoptosis of osteoblasts are identified as key factors during the regeneration of alveolar bone tissue processes. Periodontal ligament stem cells (PDLSCs) have been proved to be a possible candidate for the treatment of periodontitis due to its multiple advantages, such as increasing the regenerative capacity of bone tissue. However, the effect of exosomes derived from PDLSCs (PDLSC‐Exo) on osteoblasts remains to be further studied.Methods and MaterialsIn this work, cell proliferation, migration, osteogenic differentiation, and H2O2‐induced apoptosis were detected after cells were exposed to PDLSC‐Exo by CCK‐8, scratch wound assay, alizarin red S and alkaline phosphatase staining, real‐time PCR, flow cytometry, tunel assay, and so on. Moreover, the activation of PI3K/AKT and MEK/ERK signaling pathways was evaluated by western blotting.ResultsWe found that PDLSC‐Exo are capable of promoting hFOB1.19 cell proliferation, migration and osteogenic differentiation, inhibiting H2O2‐induced apoptosis, and activating the PI3K/AKT and MEK/ERK signaling pathways.ConclusionThese results suggest that PDLSC‐Exo may be a promising therapeutic for osteoblastic damage.

Effects of periodontal cells‐derived extracellular vesicles on mesenchymal stromal cell function

“…This suggests that further optimisation of the sEV isolation protocol is required, or that additional steps such as DNase/proteinase/RNase treatment should be applied to enhance the EV purity, in accordance with international EV study guidelines 38 . Nevertheless, sEV from all three periodontal cells was smaller than 200 nm, which was in line with previous reports for PDLCs‐sEV 24,25,46 and GFs‐sEV 19,20 . Although apoptotic bodies and microvesicles are generally considered to be larger than 200 nm, 48 it is worth noting that the EV mode of the 2.6 and 16k EV from the periodontal cells was also smaller than 200 nm.…”

“…All three EVs subtypes were internalised in BFP‐MSCs from 4 h to 7 days. sEV promoted cell proliferation and migration compared to the EV‐free group, as observed previously for PDLCs‐sEV 24,46 and GMSCs‐sEV 18 on other cell types, and upregulated osteogenic gene levels consistent with other studies showing enhance in vitro and in vivo osteogenesis mediated by PDLCs‐sEV and GF/GMSCs‐sEV 18–20,22,24,46,53,54 . When comparing the sEVs from the three periodontal cells, the present data showed superior osteogenic differentiation potential for hOBs‐sEV on BFP‐MSCs compared to hPDLCs‐ and hGFs‐sEV.…”

“…sEV promoted cell proliferation and migration compared to the EV-free group, as observed previously for PDLCs-sEV 24,46 and GMSCs-sEV 18 and in vivo osteogenesis mediated by PDLCs-sEV and GF/GMSCs-sEV. [18][19][20]22,24,46,53,54 When comparing the sEVs from the three periodontal cells, the present data showed superior osteogenic differentiation potential for hOBs-sEV on BFP-MSCs compared to hPDLCs-and hGFs-sEV. This might be expected since alveolar bone-derived hOBs have superior osteogenic potential compared to hPDLCs and hGFs, 11 although requires further investigation in vitro and in vivo to confirm.…”

“…[3,4,14]). Studies showed that sEVs derived from bone marrow-derived MSCs (BMSCs), [15][16][17] GM-SCs [18][19][20] and PDLCs [21][22][23][24][25] have demonstrated elevated osteogenesis and anti-inflammatory capability in the context of bone regeneration in vitro and in vivo. However, there have been few studies that have investigated the regenerative potential of EVs produced by alveolar bone-derived osteoblasts, as well as the comparison of the effects of hPDLCs-EVs, hGFs-EVs and hOBs-EVs on the differentiation fate of human buccal fat pad-mesenchymal stromal cells (hBFP-MSCs, a recently discovered source of multipotent MSCs within the oral cavity 26 ).…”

Proanthocyanidin enhances the endogenous regeneration of alveolar bone by elevating the autophagy of PDLSCs

“…Recent studies have shown that, under defined circumstances, PDLSCs could differentiate into chondrocytes, adipocytes, osteoblasts, cementoblast-like cells, and collagen-forming cells. 3,5 Moreover, under bacterial infection conditions, PDLSCs exhibited stronger survivability than bone marrow mesenchymal stem cells (BMSCs) as they resided in an ecological niche of periodontal tissue exposed to bacteria and inflammation. 6,7 Consequently, PDLSCs are widely recognized as reliable source of cells for achieving periodontal regeneration.…”