Autophagy is an evolutionarily conserved process essential for cellular homeostasis and human health. As a lysosome‐dependent degradation pathway, autophagy acts as a modulator of the pathogenesis of diverse diseases. The relationship between autophagy and oral diseases has been explored in recent years, and there is increasing interest in the role of autophagy in periodontal disease. Periodontal disease is a prevalent chronic inflammatory disorder characterized by the destruction of periodontal tissues. It is initiated through pathogenic bacterial infection and interacts with the host immune defense, leading to inflammation and alveolar bone resorption. In this review, we outline the machinery of autophagy and present an overview of work on the significance of autophagy in regulating pathogen invasion, the immune response, inflammation, and alveolar bone homeostasis of periodontal disease. Existing data provide support for the importance of autophagy as a multi‐dimensional regulator in the pathogenesis of periodontal disease and demonstrate the importance of future research on the potential roles of autophagy in periodontal disease.

The mineralization capability of cementoblasts is the foundation for repairing orthodontic treatment‐induced root resorption. It is essential to investigate the regulatory mechanism of mineralization in cementoblasts under mechanical compression to improve orthodontic therapy. Autophagy has a protective role in maintaining cell homeostasis under environmental stress and was reported to be involved in the mineralization process. Long noncoding RNAs are important regulators of biological processes, but their functions in compressed cementoblasts during orthodontic tooth movement remain unclear. In this study, we showed that compressive force downregulated the expression of mineralization‐related markers. LincRNA‐p21 was strongly enhanced by compressive force. Overexpression of lincRNA‐p21 downregulated the expression of mineralization‐related markers, while knockdown of lincRNA‐p21 reversed the compressive force‐induced decrease in mineralization. Furthermore, we found that autophagy was impeded in compressed cementoblasts. Then, overexpression of lincRNA‐p21 decreased autophagic activity, while knockdown of lincRNA‐p21 reversed the autophagic process decreased by mechanical compression. However, the autophagy inhibitor 3‐methyladenine abolished the lincRNA‐p21 knockdown‐promoted mineralization, and the autophagy activator rapamycin rescued the mineralization inhibited by lincRNA‐p21 overexpression. Mechanistically, the direct binding between lincRNA‐p21 and FoxO3 blocked the expression of autophagy‐related genes. In a mouse orthodontic tooth movement model, knockdown of lincRNA‐p21 rescued the impeded autophagic process in cementoblasts, enhanced cementogenesis, and alleviated orthodontic force‐induced root resorption. Overall, compressive force‐induced lincRNA‐p21 inhibits the mineralization capability of cementoblasts by impeding the autophagic process.

Background: Migration of cementoblasts to resorption lacunae is the foundation for repairing root resorption during orthodontic tooth movement. Previous studies reported that autophagy was activated by compression in periodontal ligament cells. The aim of this study was to investigate the migration of cementoblasts and determine whether autophagy is involved in the regulation of cementoblast migration under compressive force.Methods: Flow cytometry was employed to examine the apoptosis of murine cementoblasts (OCCM-30) at different compression times (0, 6, 12, and 24 hours) and magnitudes (0, 1.0, 1.5, and 2.0 g/cm 2 ). Cell proliferation was examined using the CCK-8 method. Wound healing migration assays and transwell migration assays were performed to compare the migration of cementoblasts. Chloroquine (CQ) and rapamycin were used to inhibit and activate autophagy, respectively. The level of autophagy was determined using western blotting and immunofluorescence staining. The expression of matrix metalloproteinases (MMPs) was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Results: Cell apoptosis and proliferation did not significantly change in OCCM-30 cells under mechanical compression at magnitude of 1.5 g/cm 2 for 12 hours. However, the migration of cementoblasts was significantly inhibited after the application of compressive force. MMP2, MMP9, and MMP13 mRNA expression was decreased, and MMP9 and MMP13 protein expression and secretion level were also decreased. Further, autophagic activity was inhibited in cementoblasts under compressive force. Treatment with chloroquine reduced the cellular migration, and rapamycin partially relieved the inhibition of cementoblast migration induced by the compressive force. MMP9 and MMP13 mRNA expression, protein expression, and secretion levels showed a similar trend. Conclusion:Migration of OCCM-30 cells was inhibited under compressive force partially dependent on the inhibition of MMPs, which was mediated by downregulation of autophagy. The findings provide new insights into the role of e128

Orthodontic tooth movement is achieved by periodontal tissue remodeling triggered by mechanical force. It is essential to investigate the reaction of periodontal ligament stem cells (PDLSCs) for improving orthodontic therapeutic approaches. Autophagy is an endogenous defense mechanism to prevent mechanical damage of environmental change. Long non-coding RNAs (lncRNAs) are key regulators in gene regulation, but their roles are still largely uncharacterized in the reaction of PDLSCs during orthodontic tooth movement. In this study, we showed that autophagy was significantly induced in PDLSCs under compressive force, as revealed by the markers of autophagy, microtubule-associated protein light chain 3 (LC3) II/I and Beclin1, and the formation of autophagosomes. After the application of compressive force, lncRNA FER1L4 was strongly upregulated. Overexpression of FER1L4 increased the formation of autophagosome and autolysosomes in PDLSCs, while knockdown of FER1L4 reversed the autophagic activity induced by mechanical force. In mechanism, FER1L4 inhibited the phosphorylation of protein kinase B (AKT) and subsequently increased the nuclear translocation of forkhead box O3 (FOXO3) and thus mediated autophagic cascades under compressive strain. In mouse model, the expression of Lc3 as well as Fer1l4 was increased in the pressure side of periodontal ligament during tooth movement. These findings suggest a novel mechanism of autophagy regulation by lncRNA during periodontal tissue remodeling of orthodontic treatment.

Ginsenoside Rg3 is a natural active ingredient that is extracted from Korean red ginseng root. It elevates the therapeutic effect of radiotherapy and chemotherapy, but previous studies found that the application of Rg3 is heavily limited by its low bioavailability and poor absorption via oral administration.To overcome these problems, Rg3-loaded PEG-PLGA-NPs (Rg3-NPs) were prepared by the modified spontaneous emulsification solvent diffusion (SESD) method, and the physicochemical characteristics of Rg3-NPs were investigated. We treated primary glioblastoma with 50 mM Rg3-NPs for 48h. We then used gene expression arrays (Illumina) for genome-wide expression analysis and validated the results for genes of interest by means of real-time PCR. Functional annotations were then performed using the DAVID and KEGG online tools. The results showed that the Rg3-NPs are slick and uniform, the average diameter of the nanoparticles is 75-90 nm, and their entrapment efficiency is 89.7 + 1.7%. MTT showed that the growth of cells can be significantly inhibited by Rg3-NPs in a dose-dependent manner. FCM testing showed Rg3-NPs can be released from the conjugate nanoparticle and react with the genes in the cell nuclei, causing changes in the gene molecules. We also found that cancer cells treated with Rg3-NPs undergo cell-cycle arrest at different checkpoints. This arrest was associated with a decrease in the mRNA levels of core regulatory genes BUB1, CDC20, TTK, and CENPE, as determined by microarray analysis and verified by real-time PCR. Furthermore, Rg3-NPs induced the expression of the apoptotic and antimigratory protein p53 in cell lines. The results of the present study, together with the results of earlier studies, show that Rg3-NPs target genes involved in the progression of the M-phase of the cell cycle. It is associated with several important pathways, which include apoptosis (p53). Rg3-NPs may be a potent cell-cycle regulation drug targeting the M-phase in glioblastoma cell lines.

Repair of orthodontic external root resorption and periodontal tissue dysfunction induced by mechanical force remains a clinical challenge. Cementoblasts are vital in cementum mineralization, a process important for restoring damaged cementum. Despite autophagy plays a role in mineralization under various environmental stimuli, the underlying mechanism of autophagy in mediating cementoblast mineralization remains unclear. Here we verified that murine cementoblasts exhibit compromised mineralization under compressive force. Autophagy was indispensable for cementoblast mineralization, and autophagic activation markedly reversed cementoblast mineralization and prevented cementum damage in mice during tooth movement. Subsequently, messenger RNA sequencing analyses identified periostin (Postn) as a mediator of autophagy and mineralization in cementoblasts. Cementoblast mineralization was significantly inhibited following the knockdown of Postn. Furthermore, Postn silencing suppressed Wnt signaling by modulating the stability of β‐catenin. Together our results highlight the role of autophagy in cementoblast mineralization via Postn/β‐catenin signaling under compressive force and may provide a new strategy for the remineralization of cementum and regeneration of periodontal tissue.

Repair of orthodontic external root resorption and periodontal tissue dysfunction induced by mechanical force remains a clinical challenge. Cementoblasts are vital in cementum mineralization, a process important for restoring damaged cementum and regaining healthy periodontal function. Autophagy is a vital self-renewal process for cellular homeostasis under various environmental stimuli. However, how autophagy mediated cementoblast mineralization remains unclear. Here we verified that murine cementoblasts exhibit compromised mineralization under compressive force. Autophagy was indispensable for cementoblast mineralization, and autophagic activation markedly reversed the capacity for cementoblast mineralization and cementum damage in mice. Subsequently, mRNA sequencing analyses identified periostin (Postn) as a regulator of autophagy and cementoblast mineralization. Cementoblast mineralization was significantly inhibited following knockdown of Postn. Furthermore, Postn silencing downregulated Wnt transcriptional activity by promoting ubiquitination of β-catenin. Together our results highlight autophagy as a mediator of cementoblast mineralization via Postn/β-catenin signaling under compressive force and may provide a new strategy for the remineralization of cementum and regeneration of periodontal tissue.