Gallic Acid Ameliorates the Inflammatory State of Periodontal Ligament Stem Cells and Promotes Pro-Osteodifferentiation Capabilities of Inflammatory Stem Cell-Derived Exosomes

Abstract

The slow proliferation rate and poor osteodifferentiation ability of inflammatory periodontal membrane stem cells extracted from periodontitis tissues (i-PDLSCs) account for poor efficiency in treating inflammatory bone loss. Exosomes reportedly have inducible and relatively stable components, allowing them to promote inflammatory bone repair, but obtaining i-PDLSCs exosomes with the ability to promote osteodifferentiation is challenging. In the present study, i-PDLSCs were extracted from periodontal membrane tissues of patients with severe periodontitis, and in vitro induction with gallic acid (GA) significantly promoted the proliferative activity of i-PDLSCs at a concentration of 10 mM, with TC0 of 11.057 mM and TC50 of 67.56 mM for i-PDLSCs. After mRNA sequencing, we found that GA could alleviate oxidative stress in i-PDLSCs and increase its mitochondrial membrane potential and glucose aerobic metabolism level, thus promoting the osteodifferentiation of i-PDLSCs. After exosomes of i-PDLSCs after GA induction (i-EXO-GA) were isolated by differential centrifugation, we found that 200 ug/mL of i-EXO-GA could remarkably promote the osteodifferentiation of i-PDLSCs. Overall, our results suggest that GA induction can enhance the proliferation and osteodifferentiation in primary cultures of i-PDLSCs in vitro, mediated by alleviating oxidative stress and glycometabolism levels in cells, which further influences the osteodifferentiation-promoting ability of i-EXO-GA. Overall, we provide a viable cell and exosome induction culture method for treating inflammatory alveolar defects associated with periodontitis.

Mitochondria in Multi-Directional Differentiation of Dental-Derived Mesenchymal Stem Cells

“…In our previous research, we observed a reduction in ROS levels in hPDLSCs after osteoblastic induction, which is in line with some previous studies [66,68]. Moreover, recent findings have revealed that decreased mitochondria-related ROS levels and enhanced mitochondria OXPHOS are associated with the promotion of the osteoblastic differentiation of i-PDLSCs (inflammatory periodontal ligament stem cells) by gallic acid [69]. In contrast, the loss of membrane potential of mitochondria significantly reduces the level of osteoblastic differentiation of hPDLSCs [69].…”

“…Moreover, recent findings have revealed that decreased mitochondria-related ROS levels and enhanced mitochondria OXPHOS are associated with the promotion of the osteoblastic differentiation of i-PDLSCs (inflammatory periodontal ligament stem cells) by gallic acid [69]. In contrast, the loss of membrane potential of mitochondria significantly reduces the level of osteoblastic differentiation of hPDLSCs [69]. Additionally, induced mitochondrial ROS accumulation was shown to suppress the osteoblastic differentiation of hPDLSCs, which can be reversed by FoxO1 or curcumin [70,71].…”

Dynamic hydrogel–metal–organic framework system promotes bone regeneration in periodontitis through controlled drug delivery

“…Appropriate concentrations of magnesium ions have been shown to not only directly promote bone repair to some extent [ 20 ], but also guide macrophages to polarize from the M1 phenotype to the M2 phenotype, thereby creating an immunomicroenvironment conducive to bone formation [ 21 ]. On the other hand, gallic acid (GA), a natural secondary metabolite rich in phenolic hydroxyl groups that effectively scavenges reactive oxygen species (ROS) and disrupts the cyclic generation of new free radicals [ 22 ], can regulate the bone regeneration process by its antioxidant properties [ 23 , 24 ]. Furthermore, GA exerts anti-inflammatory effects by reducing the release of pro-inflammatory cytokines and chemokines [ 25 ].…”