Journal of Oral Biosciences最新文献

{"title":"Molecular mechanism of NF-κB-mediated transcriptional activation of MMP12 in lipopolysaccharide-stimulated human dental pulp stem cells","authors":"Yishu Xiao ,&nbsp;Zhi Song ,&nbsp;Derong Zeng ,&nbsp;Yuhong Yang ,&nbsp;Weiqi Peng ,&nbsp;Qiaozhen Lin ,&nbsp;Yun Huang ,&nbsp;Wenxiang Chai ,&nbsp;Yonghui Li ,&nbsp;Xiu Zhao","doi":"10.1016/j.job.2025.100699","DOIUrl":"10.1016/j.job.2025.100699","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the molecular mechanisms through which matrix metalloprotein (MMP)12 exacerbates inflammation in pulpitis and to explore a potential regulatory axis between lipopolysaccharide (LPS)-induced MMP12 expression and activation of the nuclear factor-κB (NF-κB) signaling pathway.</div></div><div><h3>Methods</h3><div>An inflammatory pulpitis model was established using LPS-stimulated human dental pulp stem cells (hDPSCs). Transcriptomic profiling was conducted to identify differentially expressed genes between physiological and inflammatory states via RNA sequencing, with validation performed using quantitative real-time PCR (qPCR). The regulatory influence of the NF-κB pathway on MMP12 and cytokine expression was examined through western blotting and qPCR. In addition, dual-luciferase reporter assays were employed to confirm NF-κB binding motifs within the MMP12 promoter region.</div></div><div><h3>Results</h3><div>Treatment with LPS (1 μg/mL) triggered inflammatory activation in hDPSCs. Six pulpitis-associated genes, <em>MMP12, IL6, IL8, IL10, IL1β,</em> and <em>TNF-</em>α, were significantly upregulated (<em>P</em> &lt; 0.05). Inhibition of NF-κB markedly reduced MMP12 expression. Moreover, NF-κB was found to transcriptionally activate the MMP12 promoter through binding motifs located at positions −1590/−1600 bp upstream, thereby establishing an NF-κB/MMP12 signaling axis.</div></div><div><h3>Conclusion</h3><div>The NF-κB/MMP12 axis functions as a critical amplifier of inflammation in pulpitis. The data shows that MMP12 is a major mediator of pulp tissue destruction and represents a potential therapeutic target, highlighting a coordinated mechanism underlying disease progression.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100699"},"PeriodicalIF":2.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localization of high endothelial venules is important for the prognosis of patients with oral squamous cell carcinoma","authors":"Takashi Niiyama ,&nbsp;Aya Matsuda ,&nbsp;Nako Maishi ,&nbsp;Yasuhiro Hida ,&nbsp;Alam Mohammad Towfik ,&nbsp;Saki Shinohara ,&nbsp;Amane Mizuno ,&nbsp;Ren Zixiao ,&nbsp;Lihong Lin ,&nbsp;Wataru Kakuguchi ,&nbsp;Kenichiro Sakata ,&nbsp;Yoichi Ohiro ,&nbsp;Yoshimasa Kitagawa ,&nbsp;Hiroaki Suzuki ,&nbsp;Michihiro Ueda ,&nbsp;Kyoko Hida","doi":"10.1016/j.job.2025.100695","DOIUrl":"10.1016/j.job.2025.100695","url":null,"abstract":"<div><h3>Objectives</h3><div>Surgery, chemotherapy, and radiation therapy are currently used for the treatment of malignant tumors, and immunotherapy has recently been established as the fourth method for treating cancer. Therefore, cancer cells and their surrounding microenvironments have been the focus of attention. High endothelial venules (HEVs) that mediate lymphocyte extravasation into lymphoid organs have been reported in cancerous tissues. However, the role of HEVs remains controversial. In this study, the clinical significance of HEVs in patients with oral squamous cell carcinoma (OSCC) was examined.</div></div><div><h3>Methods</h3><div>Eighty-three patients with OSCC of the tongue who had surgery as initial treatment were included. HEVs and lymphocytes were immunohistochemically stained, and their numbers and localization were evaluated.</div></div><div><h3>Results</h3><div>The prognosis significantly improved in patients with a high number of HEVs. Additionally, localization of HEVs to the tumor margins was associated with a good prognosis. Patients with localized infiltration of CD8-positive cells at the tumor margin had a significantly better prognosis, although no correlation was observed between the number of CD8-positive cells around the HEVs and the prognosis. Cox proportional hazards model revealed that TNM Stage, localization of HEVs, and localization of CD8-positive cells are prognostic factors affecting disease-free survival in patients with OSCC.</div></div><div><h3>Conclusions</h3><div>The localization of HEVs and CD8-positive cells affect the prognosis of patients with OSCC and they are beneficial prognostic factors.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100695"},"PeriodicalIF":2.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial profiling of bold green tea bottled beverages: A screening experiment","authors":"Manami Imai ,&nbsp;Miho Kawachi ,&nbsp;Anna Wakui ,&nbsp;Misato Miyazawa ,&nbsp;Mirai Sekiguchi ,&nbsp;Yuki Kato ,&nbsp;Haruna Sato ,&nbsp;Yuka Naruse ,&nbsp;Nanami Asano ,&nbsp;Momoko Morohashi ,&nbsp;Hiroto Sano ,&nbsp;Yuki Abiko ,&nbsp;Jumpei Washio ,&nbsp;Kaori Tanaka ,&nbsp;Nobuhiro Takahashi ,&nbsp;Takuichi Sato","doi":"10.1016/j.job.2025.100697","DOIUrl":"10.1016/j.job.2025.100697","url":null,"abstract":"<div><h3>Objectives</h3><div>To explore the storage potential and drinking safety of leftover bottled tea beverages from various manufacturers after directly drinking from the bottle, we conducted a screening experiment on the growth of salivary bacteria in plastic bottles of bold green tea.</div></div><div><h3>Methods</h3><div>Resting whole saliva (n = 14) was collected from each participant (aged 19–25 years). The saliva samples (1.0 mL of each diluted saliva sample [5.0 × 10⁵ CFU/mL]), were inoculated into plastic bottles containing 280 mL of green tea, which included six types of bold green tea beverages. The bottles were stored at 37 °C for 24 h; subsequently, 1.0 mL of each sample was inoculated onto a blood agar plate and incubated anaerobically at 37 °C. Genomic DNA was extracted from the resulting individual colonies and the bacterial species were identified by 16S rDNA sequencing.</div></div><div><h3>Results</h3><div>More than 60 % of the samples of six types of bold green tea beverages, Bold Oi Ocha®, Suntory Bold Green Tea Iyemon®, Bold Oi Ocha Premium Strong®, Healthya®, Bold Ayataka®, and Catechin Green Tea® showed low bacterial levels (&lt;10³ CFU/mL) after 1 day of storage. However, in some cases, former members of the genus <em>Lactobacillus</em>, such as <em>Limosilactobacillus</em> and <em>Lactiplantibacillus</em> spp., were specifically detected as the predominant bacteria (37.6–100 %), although these bacteria usually account for the minority among the oral microbiome.</div></div><div><h3>Conclusions</h3><div>Although the antibacterial effects of catechins may have affected the total bacterial counts and compositions, no clear correlation was observed between total tea catechin concentrations and total bacterial growth inhibitory effects.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100697"},"PeriodicalIF":2.3,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural features of the articular disc of the rat temporomandibular joint: Fibrocartilage or dense fibrous lamina?","authors":"Shunichi Shibata ,&nbsp;Masami Takahashi ,&nbsp;Toru Shibui ,&nbsp;Yuri Seki-Kishimoto ,&nbsp;Masaki Takechi ,&nbsp;Kazuharu Irie","doi":"10.1016/j.job.2025.100694","DOIUrl":"10.1016/j.job.2025.100694","url":null,"abstract":"<div><h3>Objectives</h3><div>The structure of the temporomandibular joint (TMJ disc) articular disc as a dense fibrous lamina or fibrocartilage is an ongoing debate. To clarify this, we investigated TMJ disc cells in 3- to 20-week-old rats from the perspectives of general histology, ultrastructure, immunohistochemistry, and <em>in situ</em> hybridization.</div></div><div><h3>Methods</h3><div>Sections from paraffin-embedded TMJ discs were immunohistochemically stained using antibodies against aggrecan and collagen type II. Expression of <em>Acan</em> and <em>Col2a1</em> mRNA was analyzed by <em>in situ</em> hybridization using antisense cRNA probes. Other samples were analyzed by transmission electron microscopy.</div></div><div><h3>Results</h3><div>Chondrocyte-like cells were visualized on the most medial aspect of the anterior band at 20 weeks. Transmission electron microscopy revealed that these cells were structurally similar to chondrocytes (termed “morphological chondrocytes”) but with less abundant rough endoplasmic reticulum and low expression of <em>Acan</em> and <em>Col2a1</em> mRNA. Immunoreactivity for aggrecan and collagen type II was sparse in the extracellular matrix, but the areas of positivity were narrow. Immunoreactivity for hypoxia-inducible factor-1α was detected in the morphological chondrocytes and CD31-positive capillaries did not enter the disc, indicating an enhanced hypoxic environment in this region.</div></div><div><h3>Conclusions</h3><div>The presence of morphological chondrocytes in the articular disc region indicates an adaptation to the hypoxic environment rather than increased synthesis of cartilaginous matrix synthesis; hence, the rat TMJ disc can be regarded, in general, as a dense fibrous lamina rather than consisting of fibrocartilage.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100694"},"PeriodicalIF":2.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning approaches for pathological image classification","authors":"Masayuki Tsuneki","doi":"10.1016/j.job.2025.100696","DOIUrl":"10.1016/j.job.2025.100696","url":null,"abstract":"<div><h3>Background</h3><div>Computer-aided diagnosis using deep learning has emerged as a transformative tool in pathology that enables the automated and consistent interpretation of whole slide images. Among the key tasks in pathological image analysis, classification-based deep learning models have shown promise in distinguishing cancer subtypes and predicting genetic or molecular features. However, challenges remain due to the limited availability of high-quality labeled datasets, particularly for rare cancers, which hinders the widespread applicability of conventional data-driven approaches.</div></div><div><h3>Highlight</h3><div>The methodology for developing classification-based deep learning models involves data preparation, annotation strategies, training techniques, and performance evaluation. Core supervised learning approaches are used alongside convolutional and recurrent neural networks to enhance classification performance. In scenarios in which training datasets are scarce, transfer learning serves as an effective strategy to improve the model training efficiency. In addition, this review introduces emerging techniques such as the use of simulators to generate synthetic data and formula-driven approaches that simulate realistic scenarios, with the aim of overcoming the limitations of conventional training datasets. Visualization tools such as probability heatmaps are critical for model interpretability and validation.</div></div><div><h3>Conclusion</h3><div>Classification-based deep learning models are expected to play an increasing role in precision medicine by expanding capabilities beyond diagnosis to include prognostic prediction and treatment decision making. With innovations in augmented intelligence, deep learning models can comprehensively support clinicians across the diagnostic and therapeutic spectrum, particularly in an era of increasing demand and limited human resources in pathology.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100696"},"PeriodicalIF":2.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges and prospects for popularizing cell therapy in the dentistry in Japan","authors":"Morikuni Tobita,&nbsp;Anna Arita","doi":"10.1016/j.job.2025.100692","DOIUrl":"10.1016/j.job.2025.100692","url":null,"abstract":"<div><h3>Background</h3><div>Regenerative medicine is actively used in dentistry in Japan and mesenchymal stromal cell (MSC) therapy shows promising potential. Despite the growing interest and some clinical and private practice applications, the adoption of MSC-based therapies remains limited. In this study, we report the current status of cell therapy in dentistry in Japan and discuss the challenges in popularizing cell therapy and the future direction of dental regenerative medicine.</div></div><div><h3>Highlights</h3><div>As of May 2025, MSCs were being used for oral tissue regeneration in clinical research and private practice. Dental pulp is the primary source of MSCs, followed by adipose tissue and bone marrow. Approximately 50 private practice dental clinics in Japan offer MSC-based therapies, with most outsourcing cell processing. Current challenges in ensuring the safety and validity of cell therapy in dentistry are: 1) limited verification of safety and efficacy for specific diseases before offering private practice and 2) lack of appropriately collected clinical data to support evidence-based practice.</div></div><div><h3>Conclusion</h3><div>To safely expand regenerative medicine in dentistry, stronger support for dental clinics is essential. This includes closer collaboration with academic institutions and the systematic collection of clinical data to ensure safety and efficacy.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100692"},"PeriodicalIF":2.3,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast growth factor 2 promotes matrix vesicle-mediated mineralization of human umbilical cord perivascular cells by regulating phosphate metabolism","authors":"Sakurako Asada ,&nbsp;Risako Chiba-Ohkuma ,&nbsp;Takeo Karakida ,&nbsp;Ryuji Yamamoto ,&nbsp;Shun Nonoyama ,&nbsp;Kazuhiro Gomi ,&nbsp;Takatoshi Nagano ,&nbsp;Yasuo Yamakoshi","doi":"10.1016/j.job.2025.100693","DOIUrl":"10.1016/j.job.2025.100693","url":null,"abstract":"<div><h3>Objectives</h3><div>We aimed to investigate the role of fibroblast growth factor 2 (FGF2) in promoting osteogenic differentiation and mineralization of human umbilical cord perivascular cells (HUCPVCs) and to elucidate the underlying molecular mechanisms, particularly the matrix vesicle-mediated mineralization pathway.</div></div><div><h3>Methods</h3><div>HUCPVCs were cultured under osteogenic conditions with or without FGF2 in the presence of activated vitamin D₃, LDN-193189, and transforming growth factor β1. Mineralization was assessed using alkaline phosphatase (ALP) activity assay, Alizarin Red S staining, ALP staining, and calcium quantification. The selective FGF receptor inhibitor LY2874455 and exogenous tissue-non-specific ALP (TNAP) were used to evaluate the effects of FGF2. Transcriptomic analysis and expression profiling of matrix vesicle-mediated mineralization- and myofibroblast-related markers were performed using next-generation sequencing (NGS), quantitative polymerase chain reaction, and immunofluorescence staining. Extracellular pyrophosphate (PPi) was quantified using colorimetric assays. Additionally, the mineralization capacity of HUCPVCs was assessed on titanium and zirconia disks.</div></div><div><h3>Results</h3><div>FGF2 significantly enhanced ALP activity and mineralization, which were abrogated by LY2874455. FGF2 upregulated TNAP and phosphate transporter 1 while suppressing ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and alpha-smooth muscle actin expression. In HUCPVCs cultured without FGF2, elevated ENPP1 and PPi levels correlated with reduced mineralization, which was rescued by supplementation with TNAP. NGS revealed upregulation of matrix vesicle-mediated mineralization-related genes. Significant mineralization was observed in HUCPVCs cultured with FGF2 on titanium and zirconia disks.</div></div><div><h3>Conclusions</h3><div>FGF2 enhances HUCPVC-mediated mineralization via dual regulation: ALP induction and ENPP1–PPi suppression. These findings support the therapeutic potential of FGF2 in bone tissue engineering and implant surface integration.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100693"},"PeriodicalIF":2.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement components C1r and C1s promote oral squamous cell carcinoma cell proliferation","authors":"Thinh Thi Kim Truong ,&nbsp;Tatsufumi Fujimoto ,&nbsp;Shinsuke Fujii ,&nbsp;Kari J. Kurppa ,&nbsp;Kana Hasegawa ,&nbsp;Yudai Tajiri ,&nbsp;Masafumi Moriyama ,&nbsp;Tamotsu Kiyoshima","doi":"10.1016/j.job.2025.100691","DOIUrl":"10.1016/j.job.2025.100691","url":null,"abstract":"<div><h3>Objectives</h3><div>Oral squamous cell carcinoma (OSCC), the most frequent cancer of the oral cavity, mostly arises from the mucosal epithelium and rarely from the odontogenic epithelium. However, it is unclear whether they share the same mechanisms of OSCC development. Recently, we clarified comprehensive gene expression patterns in pathological specimens of two types of OSCC (odontogenic epithelial and mucosal epithelial origin). In addition, the enrichment analysis demonstrated that the \"COMPLEMENT\" gene set was elevated in these tumor lesions. However, the role of this system in OSCC tumorigenesis remains unclear. Here, we aimed to investigate the involvement of complement components in OSCC development.</div></div><div><h3>Methods</h3><div>siRNA and shRNA were used to examine OSCC cell proliferation <em>in vitro</em> and <em>in vivo</em> and assess activation of intracellular signaling using western blotting technics. An MEK1/2-specific inhibitor was used to verify its effects on the expression of C1r and/or C1s, components of the classical complement pathway. C1s expression in OSCC pathological specimens was investigated using immunohistochemical analysis.</div></div><div><h3>Results</h3><div>C1r and/or C1s expression regulated ERK and/or AKT activation and promoted OSCC cell growth. In addition, activated ERK regulated the expression of C1r and C1s via a negative-feedback loop. Immunohistochemically, C1s was expressed in the tumor lesions and frequently showed high expression levels of both phosphorylated ERK and Ki-67, but not in the non-tumor regions of OSCC specimens.</div></div><div><h3>Conclusions</h3><div>The complement system may be a common molecular mechanism for OSCC tumorigenesis, which arises from different origins: odontogenic and mucosal epithelium. Elevated C1r/C1s expression contributes to OSCC cell proliferation.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100691"},"PeriodicalIF":2.3,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Gremlin1 reduces osteoclast activation and alleviates inflammation-induced bone loss by disrupting the NF-κB signaling pathway","authors":"Yuting Wang ,&nbsp;Wenlan Li ,&nbsp;Yifei Tang ,&nbsp;Wenli Mu ,&nbsp;Mingfei Wang ,&nbsp;Wenjing Liu ,&nbsp;Xiaomei Guo ,&nbsp;Tiezhou Hou ,&nbsp;Xiaoyue Guan","doi":"10.1016/j.job.2025.100686","DOIUrl":"10.1016/j.job.2025.100686","url":null,"abstract":"<div><h3>Objectives</h3><div>Gremlin1 plays a crucial role in the development of various inflammatory diseases that cause bone loss, including periodontitis and apical periodontitis (AP). The impact of Gremlin1 on osteoclast activation and its mechanisms in the progression of inflammation-induced bone loss remains unclear. This study aimed to investigate the role of Gremlin1 in the activation of osteoclasts within the inflamed peri-apical region and its possible mechanism.</div></div><div><h3>Methods</h3><div>A local Gremlin1 knock-down AP animal model was established. Micro-computed tomography and hematoxylin and eosin staining were used to assess the volume of bone defects and the extent of inflammatory infiltration. Tartrate-resistant acid phosphatase staining was used to quantify osteoclast numbers and immunohistochemical staining was used to assess the expression of osteoclast differentiation-related proteins in inflamed peri-apical tissues. Subsequently, THP-1 cells with differential expression of Gremlin1 were stimulated to develop into osteoclasts and the activation of osteoclasts and variables associated with osteoclastogenesis were re-evaluated. The activation level of the NF-κB signaling pathway was examined using in vivo and in vitro models.</div></div><div><h3>Results</h3><div>Local administration of adeno-associated virus-silenced Gremlin1 to peri-apical tissues significantly inhibited alveolar bone loss. The number of osteoclasts and the expression of genes associated with osteoclastogenesis were markedly decreased. The in vivo and in vitro experimental findings were consistent and revealed that the silencing of Gremlin1 effectively suppresses activation of the NF-κB signaling pathway. Conversely, over-expression of Gremlin1 may facilitate activation of this pathway.</div></div><div><h3>Conclusion</h3><div>Gremlin1 regulates osteoclasts differentiation through the NF-κB signaling pathway, thereby attenuating the development of inflammation-induced bone loss.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100686"},"PeriodicalIF":2.3,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spermidine enhances Immunoglobulin A secretory capacity in rat salivary glands: An ex vivo study","authors":"Yuta Hosomi ,&nbsp;Yuko Yamamoto ,&nbsp;Ryuta Endo ,&nbsp;Masahiro Sugimoto ,&nbsp;Wakako Sakaguchi ,&nbsp;Shinya Fuchida ,&nbsp;Toshiya Morozumi ,&nbsp;Juri Saruta ,&nbsp;Keiichi Tsukinoki","doi":"10.1016/j.job.2025.100687","DOIUrl":"10.1016/j.job.2025.100687","url":null,"abstract":"<div><h3>Objectives</h3><div>Salivary Immunoglobulin A (IgA) plays a crucial role in mucosal immunity. However, the mechanisms that regulate its production are unclear. Spermidine (SPD), a polyamine involved in various cellular functions, has been implicated in immune modulation. In this study, we investigated the presence of SPD in rat salivary glands and its potential role in enhancing production of IgA.</div></div><div><h3>Methods</h3><div>Male Wistar rats were fed a low-polyamine diet for eight weeks. Submandibular and parotid glands were harvested and metabolomic analysis was used to determine the SPD concentration, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to evaluate gene expression related to polyamine metabolism and autophagy, enzyme-linked immunosorbent assay (ELISA) was used to quantify secretion of IgA, and immunohistochemistry was used to localize spermidine synthase (SRM).</div></div><div><h3>Results</h3><div>Metabolomic analysis revealed that the concentration of SPD was significantly higher in the submandibular gland than in the parotid gland. RT-qPCR revealed higher <em>SRM</em> and <em>LC3b</em> mRNA expression, and lower <em>Rubicon</em> expression in the submandibular gland. Ex vivo SPD supplementation significantly increased secretion of IgA from both glands. Immunohistochemistry confirmed strong SRM expression in the acinar and ductal cells of the submandibular gland.</div></div><div><h3>Conclusions</h3><div>These findings suggest that SPD is endogenously synthesized in rat salivary glands, particularly in the submandibular gland, and may enhance the ex vivo production capacity of IgA in salivary gland tissues. These results provide insights into the role of polyamines in mucosal immunity and suggest potential therapeutic applications of SPD in enhancing oral immune defense.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100687"},"PeriodicalIF":2.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144830178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}