Background: Occlusal trauma can aggravate periodontitis, but the mechanism remains unclear. Yes-associated protein (YAP), a mechanical stressor protein, may play an important role in this process. Methods: Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to detect the expression of YAP and inflammatory factors in patients with periodontitis accompanied with or without occlusal trauma. Through local administration of Porphyromonas gingivalis and composite resin bonding on maxillary molars in mice, we established periodontitis and occlusal trauma models. Treatment with or without XAV939, to inhibit YAP activation, was performed in these models. Micro-computed tomography, immunofluorescence (IF), and qRT-PCR were used to explore the YAP pathway in periodontitis with occlusal trauma. Cyclic stress and lipopolysaccharide (LPS) stimuli were applied to the L929 mouse fibroblast cell line with or without XAV939. Western blot, IF, and qRT-PCR were used to verify the in vivo results. Results: Activated dephosphorylated YAP and increased expression of inflammatory factors were observed in patients with periodontitis accompanied with occlusal trauma. In the mouse model of periodontitis with occlusal trauma, YAP transferred into the nucleus, resulting in Jun N-terminal kinases (JNK) related pro-inflammatory pathway up-regulation. L929 cell cyclic stress and LPS stimulation results confirmed the in vivo results. Application of XAV939 inhibited YAP protein dephosphorylation and reduced JNK pro-inflammatory pathway factor expression in vivo and in vitro. Conclusions: Occlusal trauma can activate YAP nuclear transfer, resulting in the up-regulation of the JNK pro-inflammatory pathway. This can be inhibited by the XAV939 YAP inhibitor.

Periodontitis is a chronic inflammatory oral disease that affects nearly 50% of all adults. Fusobacterium nucleatum (F. nucleatum) is known to be involved in the formation and development of periodontitis. Outer membrane vesicles (OMVs) harboring toxic bacterial components are continuously released during F. nucleatum growth and regulate the extent of the inflammatory response by controlling the functions of immune and non-immune cells in tissues. Macrophages are important immune cells in periodontal tissue that resist pathogen invasion and play an important role in the pathophysiological process of periodontitis. However, the role of the interaction between F. nucleatum OMVs and macrophages in the occurrence and development of periodontitis has not been studied. The purpose of this study was to clarify the effect of F. nucleatum OMVs on the polarization of macrophages and the roles of this specific polarization and F. nucleatum OMVs in the pathophysiology of periodontitis. The periodontitis model was established by inducing ligation in C57BL/6 mice as previously described. Micro-CT, RT-qPCR, hematoxylin-eosin (H&E) and tartrate acid phosphatase (TRAP) staining assays were performed to analyze the periodontal tissue, alveolar bone loss, number of osteoclasts and expression of inflammatory factors in gingival tissue. The changes in the state and cytokine secretion of bone marrow-derived macrophages (BMDMs) stimulated by F. nucleatum OMVs were observed in vivo by confocal microscopy, flow cytometry, Western blot and ELISA. Mouse gingival fibroblasts (MGFs) were isolated and then cocultured with macrophages. The effects of F. nucleatum OMVs on the proliferation and apoptosis of MGFs were analyzed by flow cytometry and lactate dehydrogenase (LDH) assays. The periodontitis symptoms of mice in the F. nucleatum OMVs + ligation group were more serious than those of mice in the simple ligation group, with more osteoclasts and more inflammatory factors (IL-1β, IL-6, and TNF-α) being observed in their gingival tissues. M0 macrophages transformed into M1 macrophages after the stimulation of BMDMs with F. nucleatum OMVs, and the M1 macrophages then released more inflammatory cytokines. Analysis of the coculture model showed that the MGF apoptosis and LDH release in the inflammatory environment were increased by F. nucleatum OMV treatment. In conclusion, F. nucleatum OMVs were shown to aggravate periodontitis, alveolar bone loss and the number of osteoclasts in an animal model of periodontitis. F. nucleatum OMVs promoted the polarization of macrophages toward the proinflammatory M1 phenotype, and the inflammatory environment further aggravated the toxicity of F. nucleatum OMVs on MGFs. These results suggest that M1 macrophages and F. nucleatum OMVs play roles in the occurrence and development of periodontitis.

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Pulpitis is one of the common diseases indicated by the department of stomatology that is located in the tooth and contains abundant nerve vessels. In order to evaluate the pain degree and functional recovery of patients after treatment by visual analogue pain scale (VAS) and temporomandibular joint function score, a retrospective analysis was performed on 128 patients diagnosed with pulpitis who received root canal treatment in the department of stomatology from January 2020 to March 2021. The results show that 3%NaClO combined with 0.9% sodium chloride injection can effectively relieve the pain degree of patients after treatment, and the antibacterial effect is significantly better than 3%H2O2 combined with 0.9% normal saline. Meanwhile, it can effectively improve the temporomandibular joint function and reduce the recurrence rate, which has good clinical application value.

Large doses of oral Propranolol to treat severe IHs patients had great clinical results. The treatment can shorten the natural course of IHs, making it a possible first choice for treatment.