Objectives: NLRP3 inflammasome is a critical part of the innate immune system and plays an important role in a variety of inflammatory diseases. However, the effects of NLRP3 inflammasome on periodontitis have not been fully studied.Materials and methods: We used ligature‐induced periodontitis models of NLRP3 knockout mice (NLRP3^KO) and their wildtype (WT) littermates to compare their alveolar bone phenotypes. We further used Lysm‐Cre/Rosa^nTnG mouse to trace the changes of Lysm‐Cre⁺ osteoclast precursors in ligature‐induced periodontitis with or without MCC950 treatment. At last, we explored MCC950 as a potential drug for the treatment of periodontitis in vivo and in vitro.Results: Here, we showed that the number of osteoclast precursors, osteoclast differentiation and alveolar bone loss were reduced in NLRP3^KO mice compared with WT littermates, by using ligature‐induced periodontitis model. Next, MCC950, a specific inhibitor of the NLRP3 inflammasome, was used to inhibit osteoclast precursors differentiation into osteoclast. Further, we used Lysm‐Cre/Rosa^nTnG mice to demonstrate that MCC950 decreases the number of Lysm‐Cre⁺ osteoclast precursors in ligature‐induced periodontitis. At last, treatment with MCC950 significantly suppressed alveolar bone loss with reduced IL‐1β activation and osteoclast differentiation in ligature‐induced periodontitis.Conclusion: Our findings reveal that NLRP3 regulates alveolar bone loss in ligature‐induced periodontitis by promoting osteoclastic differentiation.

Hyaluronan synthases (HAS) control the biosynthesis of hyaluronan (HA) and critically modulate the tumor microenviroment. Cancer-associated fibroblasts (CAFs) affect the progression of a tumor by remolding the matrix. However, little is known about the role of HAS from CAFs in this process. This study aimed to determine the role of hyaluronan synthase 2 (HAS2) from CAFs in the progression of oral squamous cell carcinoma (OSCC) invasion. HAS isoforms 1, 2, and 3 in paired sets of CAFs and normal fibroblasts (NFs) were examined by real-time PCR, and the expression of HAS2 and α-SMA in OSCC tissue sections was further evaluated using immunohistochemical staining. Furthermore, we used a conditioned culture medium model to evaluate the effects of HAS2 from CAFs on the invasion and epithelial-mesenchymal transition (EMT) of the oral cancer cells Cal27. Finally, we compared the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) between CAFs and NF, and between CAFs with or without HAS2 knockdown using an antibody array and western blotting. CAFs expressed higher levels of HAS2 than the paired NFs. HAS2 expression was consistent with α-SMA-positive myofibroblasts in the stroma of OSCC, and these were significantly correlated advanced clinical stages and cervical lymph node metastasis. Knocking down HAS2 with a specific siRNA or treatment with a HAS inhibitor markedly attenuated CAF-induced invasion and EMT of Cal27 cells. Higher MMP1 and lower TIMP1 levels were detected in the supernatants of CAFs relative to NFs. Knocking down HAS2 could decrease the expression of MMP1 and increase that of TIMP1 in CAFs. HAS2 is one of the key regulators responsible for CAF-mediated OSCC progression and acts by modulating the balance of MMP1 and TIMP1.

NLRP3 inflammasome plays an important role in the pathogenesis of rheumatoid arthritis (RA). However, the post-transcriptional regulation of NLRP3 expression by miRNA in synovial macrophages is still not well understood. The aim of the study is to elucidate the mechanisms of RA with the focus on miRNAs mediated post-transcriptional regulation of the NLRP3 inflammasome. Here, we used NLRP3-deficient mice (NLRP3^KO) to cross with TNFα-transgenic mice (TNF^TG) to generate NLRP3^KO/TNF^TG mice, and compared their joint phenotypes with those of their TNF^TG and wild-type (WT) littermates at 5 months of age. In comparison to WT mice, articular bone volume and cartilage area are decreased, whereas inflammed area, eroded surface, ALP+ osteoblast number, TRAP+ osteoclast number, and the areas of RelA+F4/80+, Caspase-1+F4/80+, IL-1β+F4/80+ synoviocytes are increased in the TNF^TG mice. Knockout of NLRP3 ameliorates joint inflammation and bone damage in TNF^TG mice. Further, in TNFα-primed BMDMs, RelA positively regulates NLRP3 expression, but negatively regulates miR-30a. Additionally, miR-30a negatively mediates NLRP3 expression by directly binding to its 3ʹ UTR, suggesting a miR-30a-mediated feedforward loop acting on NLRP3. Finally, intra-articular injection of AAV-miR-30a inhibits NLRP3 inflammasome activation, reduces joint inflammation, and attenuates bone damage in TNF^TG mice. Thus, RelA/miR-30a/NLRP3 signal axis is involved in RA through regulating NLRP3 Inflammasome in macrophages.

Background: Maternally expressed 3 (MEG3), a long chain noncoding RNA (lncRNA), has verified its function as a suppressor in several kinds of cancers. However, the downstream mechanism of MEG3 in regulating the molecular mechanism of epithelial‐mesenchymal transformation (EMT) in head and neck squamous cell carcinoma (HNSCC) progression demands further investigation.Methods: Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to determine the expression level of MEG3 in HNSCC and adjacent normal tissues of 51 cases. Luciferase report assay was used to detect the correlation between miR‐421 and MEG3, and miR‐421 and E‐cadherin in HNSCC cell lines. Cell invasion and proliferation capacity were assessed through transwell and CCK8 assays. Scratch wound assay was used to assess cell migration capacity.Results: Firstly, this study demonstrated that the expression of MEG3 was significantly downregulated in HNSCC compared to adjacent normal tissues. Overexpressed MEG3 inhibited cell proliferation, migration, and invasion in vitro. Secondly, MEG3 upregulated the expression of E‐cadherin, which was instead downregulated by miR‐421. MiR‐421 was negatively regulated by MEG3 in HNSCC. Therefore, MEG3 regulated EMT by sponging miR‐421 targeting E‐cadherin in HNSCC.Conclusions: This study indicated that the MEG3‐miR‐421‐E‐cadherin axis could be a new therapeutic target for HNSCC.

Genetic variants in lncRNA H19 are associated with the risk of oral squamous cell carcinoma in a Chinese population Genetic variants in lncRNA H19 are associated with the risk of oral squamous cell carcinoma in a Chinese population