IFT80 promotes early bone healing of tooth sockets through the activation of TAZ/RUNX2 pathway.

Intraflagellar transport (IFT) proteins have been reported to regulate cell growth and differentiation as the essential functional component of primary cilia. The effects of IFT80 on early bone healing of extraction sockets have not been well studied. To investigate whether deletion of Ift80 in alveolar bone-derived mesenchymal stem cells (aBMSCs) affected socket bone healing, we generated a mouse model of specific knockout of Ift80 in Prx1 mesenchymal lineage cells (Prx1Cre ;IFT80f/f ). Our results demonstrated that deletion of IFT80 in Prx1 lineage cells decreased the trabecular bone volume, ALP-positive osteoblastic activity, TRAP-positive osteoclastic activity, and OSX-/COL I-/OCN-positive areas in tooth extraction sockets of Prx1Cre ; IFT80f/f mice compared with IFT80f/f littermates. Furthermore, aBMSCs from Prx1Cre ; IFT80f/f mice showed significantly decreased osteogenic markers and downregulated migration and proliferation capacity. Importantly, the overexpression of TAZ recovered significantly the expressions of osteogenic markers and migration capacity of aBMSCs. Lastly, the local administration of lentivirus for TAZ enhanced the expression of RUNX2 and OSX and promoted early bone healing of extraction sockets from Prx1Cre ; IFT80f/f mice. Thus, IFT80 promotes osteogenesis and early bone healing of tooth sockets through the activation of TAZ/RUNX2 pathway.

Roles of trained immunity in the pathogenesis of periodontitis.

Periodontitis is a chronic, inflammatory, and destructive disease caused by the imbalance of host immune response and dental biofilm, and has strong epidemiological and pathogenesis correlations with systemic diseases. The immune response in periodontitis involves both innate and adaptive immunity, with numerous immune cells and inflammatory pathways participating in a complex network of interactions. In the past decade, the concept of "trained immunity" has emerged, which highlights the memory characteristics of innate immunity, thus opening up a new avenue of research. There is growing interest in exploring the role of trained immunity in chronic inflammatory and metabolic diseases such as atherosclerosis and diabetes mellitus. Evidence suggests that trained immunity may also regulate the onset and progression of periodontitis, serving as a bridge between periodontitis-related comorbidities. In this review, we summarize concepts related to trained immunity and its development. Furthermore, we present current evidence that endorses the notion of trained immunity in periodontitis and analyze possible roles it may assume regarding periodontitis-associated inflammatory reactions from a cellular perspective. Finally, we discuss various clinical therapeutic strategies for periodontitis and its associated comorbidities that target trained immunity. We hope that more researchers will pay attention to this emerging concept, thereby providing deeper insights into this novel field.

Functional Polymorphisms of CTLA4 Associated with Aggressive Periodontitis in the Chinese Han Population.

BACKGROUND/AIMS: CTLA4 has been identified functioning as a protein receptor which functions as an immune checkpoint, downregulating the immune system. Susceptibility to aggressive periodontitis (AgP) is influenced by gene polymorphisms related to the immune response. In this study, we focused on SNPs in the 3'-UTR of CTLA4 among Chinese AgP patients, and investigated any further relationships between the SNPs and miRNAs. METHODS: This case-control study included 120 AgP patients and 150 healthy controls. Genotyping was used to detect allele distribution. Cell transfection and the dual luciferase reporter assay were performed to investigate the potential functions of SNPs located in the 3'UTR of CTLA4. RESULTS: The data show that patients with a history of smoking were more susceptible compared to controls, exhibiting deeper probing depth, greater attachment loss and more sites of bleeding on probing. The results of genotyping analysis revealed that individuals with the GA and AA genotypes, and with the A carrier had a decreased risk (P = 0.015, P = 0.03). Furthermore, patients with the G allele might be regulated by miR-105, which caused a down-regulation of CTLA4. The carriers of the GG genotype exhibited the worst results of attachment loss and bleeding on probing. CONCLUSION: These findings show that rs56102377 in the 3'-UTR of CTLA4 may act as a protective factor by disrupting the regulatory role of miR-105 in CTLA4 expression. Thus, our study highlighted a potential role of these polymorphisms as genetic susceptibility biomarkers of periodontitis in Chinese Han populations.

Prevalence and distribution of Aggregatibacter actinomycetemcomitans and its cdtB gene in subgingival plaque of Chinese periodontitis patients.

BACKGROUND: Aggregatibacter actinomycetemcomitans (A.actinomycetemcomitans) is an important periodontal pathogen that can participate in periodontitis and other non-oral infections. The cytolethal distending toxin (Cdt) is among the virulence factors produced by this bacterium. This study was to elucidate the distribution of A.actinomycetemcomitans and the prevalence of its cdtB gene in Chinese subjects. METHODS: A total of 255 subgingival samples were obtained from 30 subjects. Samples were collected from periodontal healthy sites as well as shallow, moderate and deep pockets. The absolute quantity of A.actinomycetemcomitans and cdtB gene were determined by real-time polymerase chain reaction. RESULTS: A.actinomycetemcomitans was detected in 92 of 105 (87.6%) samples of aggressive periodontitis (AgP) patients, in 73 of 79 (92.4%) samples of chronic periodontitis ( CP) patients and in 5 of 71 (7.0%) samples of periodontal healthy subjects. The cdtB gene was detected in 72 sites (78.3%) with AgP infected with A.actinomycetemcomitans, 54 sites (74.0%) with CP infected with A.actinomycetemcomitans and none in healthy sites infected with A.actinomycetemcomitans. In addition, quantity of A.actinomycetemcomitans and cdt gene in samples from deep pockets were significant larger than moderate, shallow and healthy sites (P < 0.05). In comparison to CP, AgP patients were infected with increased numbers of cdt genotype in deep pockets (P < 0.05). CONCLUSION: This study suggests that the cdtB gene are prevalent in A.actinomycetemcomitans, and the distribution of cdt genotype strain may be correlated with AgP and serious periodontal inflammation.

Interleukin-10 polymorphisms affect the key periodontal pathogens in Chinese periodontitis patients.

Interleukin-10 (IL-10) polymorphisms have been shown to affect IL-10 production. This study investigated the influences of IL-10 polymorphisms on the susceptibility to chronic periodontitis (CP) and aggressive periodontitis (AP), and their possible role in the quantity of subgingival bacteria Aggregatibacter Actinomycetemcomitans and Porphyromonas gingivalis. 92 CP patients, 83 AP patients and 91 periodontal healthy controls were recruited. Serum IL-10 concentration was analyzed by enzyme-linked immunosorbent assay (ELISA). Gene polymorphisms were determined by multiplex SNaPshot technique. Bacteria were quantified by real-time polymerase chain reaction with TaqMan MGB probes. Taking into account age, gender and periodontal status, IL-10-592 AA, -819 TT and ATA/ATA genotype occurred more frequently in patients with CP than in healthy controls. In CP cases, higher quantity of subgingival A. actinomycetemcomitans and lower serum IL-10 levels could be detected in homozygous ATA/ATA carriers. These findings indicate that variants in IL-10 promoter gene were not only associated with predisposition to chronic periodontitis but also affected the subgingival number of A. Actinomycetemcomitans in a Chinese Han population.