Journal of Oral Biosciences最新文献

Objectives

This study aimed to investigate the regulatory mechanisms governing dental mesenchymal cell commitment during tooth development, focusing on odontoblast differentiation and the role of epigenetic regulation in this process.

Methods

We performed single-cell RNA sequencing (scRNA-seq) of dental cells from embryonic day 14.5 (E14.5) mice to understand the heterogeneity of developing tooth germ cells. Computational analyses including gene regulatory network (GRN) assessment were conducted.

We validated our findings using immunohistochemistry (IHC) and in vitro loss-of-function analyses using the DNA methyltransferase 1 (DNMT1) inhibitor Gsk-3484862 in primary dental mesenchymal cells (DMCs) isolated from E14.5 mouse tooth germs. Bulk RNA-seq of Gsk-3484862-treated DMCs was performed to identify potential downstream targets of DNMT1.

Results

scRNA-seq analysis revealed diverse cell populations within the tooth germs, including epithelial, mesenchymal, immune, and muscle cells. Using single-cell regulatory network inference and clustering (SCENIC), we identified Dnmt1 as a key regulator of early odontoblast development. IHC analysis showed the ubiquitous expression of DNMT1 in the dental papilla and epithelium. Bulk RNA-seq of cultured DMCs showed that Gsk-3484862 treatment upregulated odontoblast-related genes, whereas genes associated with cell division and the cell cycle were downregulated. Integrated analysis of bulk RNA-seq data with scRNA-seq SCENIC profiles was used to identify the potential Dnmt1 target genes.

Conclusions

Dnmt1 may negatively affect odontoblast commitment and differentiation during tooth development. These findings contribute to a better understanding of the molecular mechanisms underlying tooth development and future development of hard-tissue regenerative therapies.

Objectives

Japanese children have been shown to exhibit decreased masticatory function; however, limited evidence is available regarding the efficacy of certain food items in improving this issue. Therefore, this study examined the effects of chewing hard gummy candy on the masticatory function of Japanese children aged 6–12 years.

Methods

The study included 26 participants (10 boys and 16 girls; mean age ± standard error = 9.3 ± 0.3 years) who were asked to chew hard gummy candy twice daily for 4 weeks at home. The lip-closing force, occlusal force, and masticatory performance of the participants were recorded before commencement (T1), 4 weeks after commencement (T2), and 4 weeks after completion (T3) of the training. Statistical analyses were performed using the Wilcoxon rank-sum test or the Wilcoxon signed-rank test with Bonferroni correction.

Results

No significant differences in masticatory function by gender and age groups (defined based on mean age at T1) were observed at T1. The lip-closing and right occlusal forces increased significantly after 4 weeks of exercise, and the effects persisted for another 4 weeks after completion. The masticatory performance also improved after training, although these effects did not persist and deteriorated substantially 4 weeks after completion of the training.

Conclusions

Habitual mastication training using hard gummy candy markedly enhances masticatory function (e.g., lip-closing force, occlusal force, and masticatory performance) in Japanese children.

Objectives

The present study aimed to elucidate the pathogenesis of temporomandibular joint (TMJ) osteoarthritis (TMJ-OA) in a mouse model. We investigated morphological and histological changes in the head of mandible cartilage and early immunohistochemical (IHC) changes in transforming growth factor (TGF)-β, phosphorylated Smad-2/3 (p-Smad2/3), a TGF-β signaling molecule, and asporin.

Methods

TMJ-OA was induced in a mouse model through unilateral partial discectomy. Micro-computed tomography (micro-CT) and safranin-O staining were performed to morphologically and histologically evaluate the degeneration of the head of mandible caused by TMJ-OA. IHC staining for TGF-β, p-Smad2/3, and asporin was performed to evaluate the changes in protein expression.

Results

In the experimental group, three-dimensional (3D) morphometry revealed an enlarged head of mandible and safranin-O staining showed degeneration of cartilage tissue in the early stages of TMJ-OA compared to the control group. IHC staining revealed that TGF-β, p-Smad2/3, and asporin expression increased in the head of mandible cartilage before the degeneration of cartilage tissue, and subsequently decreased for a short period.

Conclusion

The findings suggested a negative feedback relationship between the expression of asporin and the TGF-β/Smad transduction pathway, which may be involved in the degeneration of the head of mandible in the early stages of TMJ-OA. Asporin is a potential biomarker of the early stages of TMJ-OA, which ultimately leads to the irreversible degeneration of TMJ tissues.

Background

Asthma is a common chronic inflammatory disease affecting more than 260 million people worldwide. Nocturnal exacerbations of asthma symptoms significantly affect sleep quality and contribute to the most serious asthma exacerbations, which can lead to respiratory failure or death. Although β₂-adrenoceptor agonists are the standard of care for asthma, their bronchodilatory effect for nocturnal asthma is limited, and medications that specifically target symptoms of nocturnal asthma are lacking.

Highlight

Melatonin, which is secreted by the pineal gland, plays a crucial role in regulating circadian rhythms. Peak serum melatonin concentrations, which are inversely correlated with diurnal changes in pulmonary function, are higher in patients with nocturnal asthma than in healthy individuals. Melatonin potentiates bronchoconstriction through the melatonin MT₂ receptor expressed in the smooth muscles of the airway and attenuates the bronchodilatory effects of β₂-adrenoceptor agonists, thereby exacerbating asthma symptoms. Melatonin inhibits mucus secretion and airway inflammation, potentially ameliorating asthma symptoms.

Conclusion

Melatonin may exacerbate or ameliorate various pathophysiological conditions associated with asthma. As a potential therapeutic agent for asthma, the balance between its detrimental effects on airway smooth muscles and its beneficial effects on mucus production and inflammation remains unclear. Further studies are needed to elucidate whether melatonin worsens or improves asthma symptoms.

Background

Botulinum toxin type A (BTX-A), produced by the gram-positive anaerobic bacterium Clostridium botulinum, acts by cleaving synaptosome-associated protein-25 (SNAP-25), an essential component of the presynaptic neuronal membrane that is necessary for fusion with the membrane proteins of neurotransmitter-containing vesicles. Recent studies have highlighted the efficacy of BTX-A in treating chronic pain conditions, including lower back pain, chronic neck pain, neuropathic pain, and trigeminal neuralgia, particularly when patients are unresponsive to traditional painkillers. This review focuses on the analgesic effects of BTX-A in various chronic pain conditions, with a particular emphasis on the orofacial region.

Highlight

This review focuses on the mechanisms by which BTX-A induces analgesia in patients with inflammatory and temporomandibular joint pain. This review also highlights the fact that BTX-A can effectively manage neuropathic pain and trigeminal neuralgia, which are difficult-to-treat chronic pain conditions. Herein, we present a comprehensive assessment of the central analgesic effects of BTX-A and a discussion of its various applications in clinical dental practice.

Conclusion

BTX-A is an approved treatment option for various chronic pain conditions. Although there is evidence of axonal transport of BTX-A from peripheral to central endings in motor neurons, the precise mechanism underlying its pain-modulating effects remains unclear. This review discusses the evidence supporting the effectiveness of BTX-A in controlling chronic pain conditions in the orofacial region. BTX-A is a promising therapeutic agent for treating pain conditions that do not respond to conventional analgesics.

Background

Tissue engineering has significantly progressed in developing full-thickness oral mucosa constructs designed to replicate the natural oral mucosa. These constructs serve as valuable in vitro models for biocompatibility testing and oral disease modeling and hold clinical potential for replacing damaged or lost oral soft tissue. However, one of the major challenges in tissue engineering of the oral mucosa is the identification of an appropriate scaffold with optimal porosity, interconnected porous networks, biodegradability, and biocompatibility. These characteristics facilitate cell migration, nutrient delivery, and vascularization. Various biomaterials have been investigated for constructing tissue-engineered oral mucosa models; collagen has demonstrated superior outcomes compared with other materials.

Highlight

This review discusses the different types of tissue-engineered oral mucosa developed using various materials and includes articles published between January 2000 and December 2022 in PubMed and Google Scholar. The review focuses on the superiority of collagen-based scaffolds for tissue engineering of oral mucosa, explores in vitro applications, and discusses potential clinical applications.

Conclusion

Among the various scaffold materials used for engineering the connective tissue of the oral mucosa, collagen-based scaffolds possess excellent biological properties, offering high-quality oral mucosa constructs and high resemblance to the native human oral mucosa in terms of histology and expression of various differentiation markers.

Objective

Chronic constriction injury (CCI) of the infraorbital nerve induces neuropathic pain, such as allodynia and hyperalgesia, in the orofacial area. However, the changes in the local circuits of the central nervous system following CCI remain unclear. This study aimed to identify the changes following CCI in Thy1-GCaMP6s transgenic mice.

Methods

Neural activity in the primary somatosensory cortex (S1) and motor cortex (M1) following whisker stimulation was assessed using in vivo Ca²⁺ imaging. CCI-induced changes in responses were analyzed.

Results

Before CCI, whisker stimulation induced a greater Ca²⁺ response in the contralateral S1 than in the ipsilateral S1 and contralateral M1. The peak Ca²⁺ response amplitude in the bilateral S1 and contralateral M1 decreased two days after CCI compared to before CCI. Decreased Ca²⁺ response amplitude in these regions was observed until four days after CCI. Seven days after CCI, the Ca²⁺ response amplitude in the contralateral S1 decreased, whereas that in the ipsilateral S1 and contralateral M1 recovered to control levels.

Conclusion

These results suggest that neural activity in regions receiving excitatory inputs via corticocortical pathways recovers earlier than in regions receiving thalamocortical inputs. (185/250 words)

Objectives

Streptococcus pneumoniae, a human respiratory pathogen, causes diseases with severe morbidity and mortality rates worldwide. The two-component regulatory system (TCS) is an important signaling pathway that enables regulation of gene expression in response to environmental cues, thereby allowing an organism to adapt to a variety of host niches. Here we examined the contribution of pneumococcal TCS08 to bacterial colonization, the development of pneumonia, and pulmonary dysfunction.

Methods

We employed an hk08 knockout mutant (Δhk08) with a background of the TIGR4 wild-type (WT) strain to verify whether TCS08 is associated with bacterial colonization and the development of pneumonia in a murine infection model. To clarify the association of hk08 inactivation-induced phenotypic changes with their virulence, we examined pneumococcal capsule production, colony morphology, and surface-displayed protein profiles.

Results

Pneumococcal TCS08 was involved in bacterial colonization in the respiratory tract. Interruption of the signaling pathway of TCS08 by hk08 inactivation impaired mouse survival and increased the bacterial burden within the respiratory tract. Furthermore, a histopathological examination revealed massive inflammatory cell infiltration, edema formation, and diffuse alveolar damage in the lung tissues of mice infected with Δhk08 versus the WT or complemented strain. Interestingly, virulence-associated phenotype changes, including capsule production, increased chain length, and surface-displayed protein profile, were observed in the Δhk08 strain.

Conclusions

The present findings indicate that TCS08 contributes to pneumococcal colonization and pulmonary dysfunction by assisting adaptation to the respiratory tract milieu, leading to the development of pneumonia.

Background

Oral ulcerative mucositis (OUM) is common in patients with cancer, particularly in those undergoing chemoradiation therapy. The effective management of OUM is crucial for continuous cancer care and patient well-being. Recent studies have advanced our understanding of the causes, leading to clinical trials toward novel treatments. This review focuses on the contemporary therapeutic landscape, and provides the latest insights into the mechanisms of mucosal healing and pain.

Highlights

Management strategies for OUM in patients with cancer include maintaining good oral hygiene, reducing mucosal irritation against radiation, and using various topical analgesic treatments, including herbal medicines. However, the current management practices have limitations that necessitate the development of more efficacious and novel treatments. Molecular research on transient receptor potential (TRP) channels in the oral mucosa is crucial for understanding the mechanisms of wound healing and pain in patients with OUM. Targeting TRPV3 and TRPV4 can enhance wound healing through re-epithelialization. The suppression of TRPV1, TRPA1, and TRPV4 may be effective in alleviating OUM-induced pain.

Conclusion

Research advancements have improved our understanding and potentially led to novel treatments that offer symptomatic relief. This progress highlights the importance of collaborations between clinical researchers and scientists in the development of innovative therapies.