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Intracellular signaling complexes of the innate immune system orchestrate the development of inflammation. Porphyromonas gingivalisis a commensal bacterium that induces periodontal pyroptosis. The transcription factor Dec1 can regulate the expression of inflammatory molecules. In this study, we investigated whether a deficiency of Dec1 activates/represses Caspase-1 and/or Gasdermin-D in periodontal pyroptosis, resulting in the release of the proinflammatory mediator interleukin-1β. Dec1 expression in human periodontal ligament fibroblasts (HPDLFs) treated with P. gingivalislipopolysaccharide (LPS) was assessed and pyroptosis activation was determined by microscopy, qRT-PCR and Western blot analysis. Moreover, a siRNA targeting Dec1 was introduced into HPDLFs to determine the function of Dec1 in periodontal pyroptosis and a Dec1-deficient experimental mouse model of periodontitis was used. Treatment of HPDLFs with P. gingivalisLPS-stimulated levels of cleaved-Caspase-1 and cleaved-GSDMD and increased levels of phosphorylated NF-κB and interleukin-1β. In contrast, Dec1 knockdown maintained cellular homeostasis with low levels of pyroptosis. Treatment with P. gingivalisalleviated periodontal pyroptosis in PDLFs of wild-type mice and a Dec1 deficiency subsequently repressed the inflammatory effect of P. gingivalis. These results reveal for the first time the novel function of Dec1 in periodontal pyroptosis, suggesting that Dec1 is a crucial target to prevent periodontal inflammation.

A practical and atom-economic protocol for the stereoselective preparation of various 1,4- and 1,3-diene skeletons through iridium-catalyzed directed olefinic C–H allylation and alkenylation of NH-Ts acrylamides in water was developed. This reaction tolerated a wide scope of substrates under simple reaction conditions and enabled successful gram-scale preparation. Furthermore, an asymmetric variant of this reaction giving enantioenriched 1,4-dienes was achieved employing a chiral diene–iridium complex as the catalyst.

Background:This review assesses the associations of interleukin‐8 gene (IL‐8) −251A/T (rs4073) and −845T/C (rs2227532) polymorphisms with susceptibility to periodontitis. Methods:Several electronic databases were searched for eligible articles. Twelve studies involving 2,233 cases and 2,655 controls were retrieved and analyzed. Odds ratios (ORs) along with 95% confidence intervals (CIs) were calculated to assess the strength of relationship between the IL‐8polymorphisms and periodontitis risk. Results:No significant association was found for IL‐8−251A/T polymorphism with periodontitis in the overall analysis and stratification by periodontitis type and smoking status. Subgroup analysis by ethnicity revealed that −251A/T T allele and TT genotype were associated with decreased risk of periodontitis in a Brazilian mixed population (T allele versus A allele: OR 0.80, 95% CI 0.68 to 0.94, Pheterogeneity= 0.30; TT versus AA: OR 0.65, 95% CI 0.46 to 0.93, Pheterogeneity= 0.39; TT versus AA/AT: OR 0.58, 95% CI 0.35 to 0.98, Pheterogeneity= 0.01). In addition, −251A/T T allele was associated with increased periodontitis risk in Asians. Pooled estimates showed that the −845T/C polymorphism was associated with periodontitis susceptibility in overall analysis and the chronic periodontitis subgroup. In addition, marginal associations were observed between −845T/C polymorphism and periodontitis in a Brazilian mixed population. Moreover, this association was also confirmed to be significant in Brazilian non‐smokers. Conclusion:This meta‐analysis indicated that both IL‐8−251A/T and −845T/C polymorphisms may be involved in the development of periodontitis in a Brazilian mixed population, whereas the −251A/T allele T appeared to be a risk factor for periodontitis in Asians.

MicroRNAs are emerging as critical post-transcriptional modulators in bone remodeling, regulating the functions of osteoblasts and osteoclasts. Intercellular crosstalk between osteoblasts and osteoclasts is mediated by miR-21 that controls the bone homeostasis response, providing potential targets for the maintenance of osteoblast function. The aim of this study was to investigate the effects of miR-21 on osteoblast function, and to explore the underlying mechanism. Increased alkaline phosphatase (ALP) activity and accelerated matrix mineralization was observed in mouse pre-osteoblast MC3T3-E1 cells compared with the non-induction (control) group. MiR-21 positively regulates osteogenic differentiation and mineralization by facilitating the expression of key osteogenic factors (ALP, Runx2, Osteopontin (OPN), Osterix (OSX) and Mef2c) in MC3T3-E1 cells. Furthermore, a deficiency of miR-21 suppresses the expression of those factors at both the mRNA and protein levels, indicating that miR-21 is a positive regulator of osteoblastic differentiation. H-E staining, Azan staining, Masson's Trichrome staining and Toluidine blue staining were performed in jaw and femur tissues of miR-21 knockout (miR-21KO) and wild-type (WT) mice. Immunohistochemical staining revealed substantially lower levels of ALP, Runx2 and OSX expression in jaw and femur tissues of miR-21KO mice. A similar trend was observed in femur tissues using quantitative real-time (RT) PCR. A total of 17 osteogenesis-related mRNAs were found to be differentially expressed in miR-21KO femur tissues using Mouse Gene Expression Microarray analysis. GeneSpring and Ingenuity Pathway Analysis revealed several potential target genes that are involved in bone remodeling, such as IL-1β and HIF-1α. Several important pathways were determined to be facilitators of miR-21, which provides a reliable reference for future studies to elucidate the biological mechanisms of osteoblast function. Taken together, these results lead us to hypothesize a potential role for miR-21 in regulating osteoblast function, thus representing a potential biomarker of osteogenesis.

Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis; however, the underlying molecular mechanism remains largely unknown. Msx1is an anteriorly expressed transcription repressor required for palate development. Here, we investigate the role of Msx1in regional patterning of the secondary palate. The Wnt1-Cre-mediated expression of Msx1(RosaMsx1Wnt1-Cre) throughout the palatal mesenchyme leads to a cleft palate in mice, associated with aberrant cell proliferation and cell death. Osteogenic patterning of the hard palate in RosaMsx1Wnt1-Cremice is severely impaired, as revealed by a marked reduction in palatine bone formation and decreased expression of the osteogenic regulator Sp7. Overexpression and knockout of Msx1in mice show that the transcription repressor promotes the expression of the anterior palate-specific Alx1 but represses the expression of the medial-posterior palate genes Barx1, Meox2, and Tbx22. Furthermore, Tbx22constitutes a direct Msx1target gene in the secondary palate, suggesting that an Msx1 can directly repress the expression of medial-posterior specific genes. Finally, we determine that Sp7is downstream of Tbx22in palatal mesenchymal cells, suggesting that a Msx1/Tbx22/Sp7axis participates in the regulation of palate development. Our findings unveil a novel role for Msx1in regulating the anterior-posterior growth and patterning of the secondary palate.