Journal of Oral Biosciences最新文献

{"title":"Intentionally perforating the pulp chamber floor promotes M2 macrophage polarization in the dental pulp following tooth replantation in mice","authors":"Hiroto Sano ,&nbsp;Kuniko Nakakura-Ohshima ,&nbsp;Angela Quispe-Salcedo ,&nbsp;Yasuo Okada ,&nbsp;Takuichi Sato ,&nbsp;Hayato Ohshima","doi":"10.1016/j.job.2025.100681","DOIUrl":"10.1016/j.job.2025.100681","url":null,"abstract":"<div><h3>Objectives</h3><div>Perforation of the pulp floor prior to tooth replantation promotes tertiary dentin formation and reduces bonelike tissue formation in the pulp cavity. However, the mechanisms remain largely unclear. This study aimed to elucidate the effects of this method on macrophage dynamics and angiogenesis in dental pulp.</div></div><div><h3>Methods</h3><div>The bilateral maxillary first molars of TetOP–H2B–GFP mice were extracted. The left molar was immediately replanted, serving as the control group (CG), whereas the pulp floor of the right molar was perforated using a tungsten carbide bur prior to tooth replantation, serving as the experimental group (EG). Immunohistochemical analysis of F4/80, CD206, erythroblast transformation-specific-related gene (ERG), and GFP was performed on days 3, 5, and 7.</div></div><div><h3>Results</h3><div>The F4/80-positive area in the coronal pulp of the CG on days 3 and 7 was larger than that of the EG. The area of CD206 positivity, a specific marker of M2 macrophages, in the coronal pulp of the EG on day 7 was larger than that of the CG. The number of cells positive for ERG, a transcription factor expressed in vascular endothelial cells, in the coronal pulp of the EG on days 5 and 7 was higher than that of the CG. GFP-positive cells were distributed around the pulp floor on day 5 of the EG.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that perforation of the pulp chamber floor prior to tooth replantation induces early revascularization and vascular stabilization as well as promoting M2 macrophage polarization in the coronal pulp.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 3","pages":"Article 100681"},"PeriodicalIF":2.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656578","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":"The unique molecular signature of TMJ as compared to the knee, demonstrates its susceptibility to osteoarthritis","authors":"Rajnikant Dilip Raut ,&nbsp;Chumki Choudhury ,&nbsp;Amit Kumar Chakraborty ,&nbsp;Harpreet Singh ,&nbsp;Pushkar Mehra ,&nbsp;Louis Gerstenfeld ,&nbsp;Alejandro Almarza ,&nbsp;Manish V. Bais","doi":"10.1016/j.job.2025.100680","DOIUrl":"10.1016/j.job.2025.100680","url":null,"abstract":"<div><h3>Objectives</h3><div>Osteoarthritis (OA) is a debilitating joint disease that affects millions of people worldwide, with prominent effects on the temporomandibular joints (TMJs) and knee. Despite its prevalence, TMJ-OA remains understudied. This study investigated the transcriptional signature of the TMJ compared to that of the knee and explored transcriptional differences in the medial and superficial layers of TMJ-OA.</div></div><div><h3>Methods</h3><div>TMJ and knee tissue samples were collected from 6-month-old C57BL/6 J mice. TMJ superficial and medial layer cartilage from goats were collected, separated, and treated with interleukin (IL)-1β. All samples were subjected to bulk RNA sequencing, followed by differential expression and gene-set enrichment analyses.</div></div><div><h3>Results</h3><div>A total of 4031 protein-coding genes were identified that were differentially expressed in the TMJ compared to the knee, with significant enrichment of neuronal system genes and lower enrichment of innate immune system genes. Key OA biomarkers (<em>Mmp13, Postn</em>, and <em>Col1a1</em>) were more highly expressed in the TMJ, indicating higher vulnerability to OA development. IL-1β treatment of goat TMJ chondrocytes mimicked the natural TMJ-OA-like transcriptional changes and immune responses, which are also observed in a rabbit TMJ-OA model. These results validated the <em>in vitro</em> goat TMJ-OA model. The IL-1β-treated goat TMJ medial cartilage layer was enriched with OA-associated transcription factors, senescence genes, and epigenetic regulators.</div></div><div><h3>Conclusions</h3><div>This study demonstrated the unique transcriptomic signature of the TMJ compared to that of the knee, identifying differential vulnerabilities to OA- and pain-related genes. These findings provide valuable insights into the molecular mechanisms and therapeutic target selection for TMJ-OA treatment.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 3","pages":"Article 100680"},"PeriodicalIF":2.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633794","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":"Complete genome sequence of a tetracycline-resistant Streptococcus mutans strain carrying the tet(M) gene","authors":"Saki Nishihama ,&nbsp;Yujin Suzuki ,&nbsp;Tomoaki Shintani ,&nbsp;Manami Tsunoi ,&nbsp;Junzo Hisatsune ,&nbsp;Yo Sugawara ,&nbsp;Katsuhiro Takeda ,&nbsp;Miki Kawada-Matsuo ,&nbsp;Mikihito Kajiya ,&nbsp;Motoyuki Sugai ,&nbsp;Hideki Shiba ,&nbsp;Hitoshi Komatsuzawa","doi":"10.1016/j.job.2025.100679","DOIUrl":"10.1016/j.job.2025.100679","url":null,"abstract":"<div><h3>Introduction</h3><div>Tetracyclines are widely used in dental treatment. Here, we report the genomic information of the tetracycline-resistant <em>Streptococcus mutans</em> strain, HSM45, for the first time.</div></div><div><h3>Methods</h3><div>Susceptibility to tetracycline was determined using the microdilution method. The complete genome sequence of HSM45 was determined and compared with public genome data.</div></div><div><h3>Results</h3><div>HSM45 was resistant to tetracycline. The tetracycline resistance gene <em>tet</em>(M) was carried by Tn<em>916</em>, a conjugative transposon that is widely found in Gram-positive bacteria.</div></div><div><h3>Conclusion</h3><div>This study showed that <em>S. mutans</em> can acquire tetracycline resistance and it can also be a source of horizontal transfer of resistance genes.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 3","pages":"Article 100679"},"PeriodicalIF":2.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369401","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":"Identification of a transposon variant of Porphyromonas gingivalis expressing long Mfa1 fimbriae due to mfa2 inactivation","authors":"Naoyoshi Miwa ,&nbsp;Miyuna Fujimoto ,&nbsp;Kotaro Sakae ,&nbsp;Tomohiko Iwase ,&nbsp;Makoto Hirohata ,&nbsp;Yoshikazu Naiki ,&nbsp;Kiyoshi Nishikawa ,&nbsp;Hiroyuki Nawa ,&nbsp;Yoshiaki Hasegawa","doi":"10.1016/j.job.2025.100677","DOIUrl":"10.1016/j.job.2025.100677","url":null,"abstract":"<div><h3>Objectives</h3><div>Fimbriae expressed by <em>Porphyromonas gingivalis</em>, a periodontal pathogen, play a pivotal role in biofilm formation. In the type strain ATCC 33277, Mfa1 fimbriae form short structures anchored to the cell surface by Mfa2, an outer membrane protein involved in regulation of fimbrial length. Mfa1, the major fimbrilin, is classified into three genotypic types—<em>mfa1</em>^<em>70A</em><em>, mfa1</em>^<em>70B</em>, and <em>mfa1</em>^<em>53</em>—based on gene sequence. Although strain D83T3 is classified as <em>mfa1</em>^<em>70A</em>, like ATCC 33277, it expresses a 73 kDa Mfa1. This study aimed to investigate D83T3's unique functional properties to improve <em>mfa1</em> genotyping.</div></div><div><h3>Methods</h3><div>The <em>fimA</em>-deficient ATCC 33277 strain (JI-1) was used as a reference. Mfa1 polymerization and localization were analyzed using immunoblotting. N-terminal processing was evaluated by Edman degradation. Fimbrial morphology was examined using transmission electron microscopy. The region downstream of <em>mfa1</em> was sequenced. Mfa2 expression and the presence of Mfa3–5, putative tip proteins in the fimbriae, were confirmed by immunoblotting.</div></div><div><h3>Results</h3><div>The 73 kDa Mfa1 polymer was predominantly detected in D83T3's culture supernatant. Cleavage was confirmed at the gingipain recognition site. Mfa1 fimbriae in D83T3 were longer than those in JI-1. An IS5 transposase insertion was observed between <em>mfa1</em> and <em>mfa2</em> at D83T3. Mfa2 expression was reduced in D83T3 cells, and Mfa3–5 was absent from the fimbriae.</div></div><div><h3>Conclusions</h3><div>D83T3 is a transposon insertion variant that releases abnormally long Mfa1 fimbriae extracellularly due to <em>mfa2</em> inactivation. Our study's findings offer new insights, and analysis of the <em>mfa1-mfa2</em> gene structure can complement <em>mfa1</em> genotyping for the classification of <em>P. gingivalis</em>.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 3","pages":"Article 100677"},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337144","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":"Proteolytic N-terminal processing of Mfa proteins in the periodontal pathogen Porphyromonas gingivalis","authors":"Makoto Hirohata ,&nbsp;Yoshikazu Naiki ,&nbsp;Akihiro Oishi ,&nbsp;Kiyoshi Nishikawa ,&nbsp;Richard J. Lamont ,&nbsp;Karina Persson ,&nbsp;Yoshiaki Hasegawa","doi":"10.1016/j.job.2025.100678","DOIUrl":"10.1016/j.job.2025.100678","url":null,"abstract":"<div><h3>Objectives</h3><div>The asaccharolytic bacterium <em>Porphyromonas gingivalis</em> regulates biofilm formation through Mfa1 fimbriae, composed of the major subunit Mfa1 and accessory proteins including the putative tip adhesin Mfa4. These components undergo maturation via N-terminal leader peptide cleavage by gingipains. However, the mechanisms governing fimbrial assembly remain unclear. This study examined the role of protease-dependent N-terminal processing in the maturation and incorporation of Mfa1 and Mfa4 during fimbrial biogenesis.</div></div><div><h3>Methods</h3><div>Missense mutations were introduced in the N-terminal regions of <em>mfa1</em> and <em>mfa4</em> by substituting RgpA/B- and Kgp-specific cleavage sites with alanine. Surface expression of Mfa1 in mutant cells was analyzed using ELISA. Mfa1 fimbriae were purified from parental and mutant strains via ion-exchange chromatography, and N-terminal sequences of Mfa1 and Mfa4 were determined. Antibodies targeting the Mfa4 leader peptide were used for localization studies.</div></div><div><h3>Results</h3><div>Despite alanine substitutions at RgpA/B cleavage sites, Mfa1 processing persisted, indicating compensatory cleavage by Kgp or other enzymes such as dipeptidyl peptidases. Mature Mfa1 was transported to the cell surface and incorporated into fimbriae. Only the mature form of Mfa4 was detected in the fimbriae, whereas the leader peptide was enriched in the inner membrane.</div></div><div><h3>Conclusion</h3><div>These results suggest the existence of a compensatory proteolytic network in <em>P. gingivalis</em> and emphasize the biological importance of post-translational modifications in fimbrial assembly.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 3","pages":"Article 100678"},"PeriodicalIF":2.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303256","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":"Repetitive/rhythmic masticatory muscle activity under urethane anesthesia in guinea pigs: a descriptive pilot study","authors":"Sho Katsura ,&nbsp;Yutaka Matsuura ,&nbsp;Ayano Katagiri ,&nbsp;Hiroki Toyoda ,&nbsp;Makoto Higashiyama ,&nbsp;Yuji Masuda ,&nbsp;Takafumi Kato","doi":"10.1016/j.job.2025.100673","DOIUrl":"10.1016/j.job.2025.100673","url":null,"abstract":"<div><h3>Objectives</h3><div>Rhythmic/repetitive masticatory muscle activity may occur spontaneously during cyclic alternations in unconscious brain states such as sleep. An experimental model is needed to clarify these underlying mechanisms. This study investigated jaw movements and masticatory muscle activity during cyclic state alternations under urethane anesthesia.</div></div><div><h3>Methods</h3><div>Cortical electroencephalography, electrocardiography, and nasal airflow were recorded simultaneously with jaw movements and jaw muscle electromyography activity in seven urethane-anesthetized male guinea pigs (420–594 g). Cortical brain states were divided into deactivated and activated states according to electroencephalogram (EEG) delta power. The respiratory and heart rates were quantified during the two cortical states. Rhythmic jaw movements (RJMs) were visually scored and the characteristics of masticatory electromyographic bursts were analyzed. Transient changes in cortical, cardiac, and respiratory activities were analyzed in association with RJMs.</div></div><div><h3>Results</h3><div>Cortical activity and respiratory and heart rate variabilities differed significantly between activated and deactivated states. Of 321 RJMs, 290 occurred in clusters under urethane anesthesia; The majority (73.7 %) were scored during the activated state. RJM episodes were associated with alternate lateral jaw excursion, predominantly with masseter muscle activation, and occasionally with tooth-grinding sounds. RJMs were preceded by decreases in EEG delta activity and transient increases in cardiac and respiratory activities.</div></div><div><h3>Conclusions</h3><div>Masticatory muscles may be activated repetitively and rhythmically during cyclic alternations in brain states under urethane anesthesia. Urethane-anesthetized guinea pigs are a potential experimental model for examining the mechanisms underlying the generation of RJMs in unconscious states, such as sleep bruxism.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 3","pages":"Article 100673"},"PeriodicalIF":2.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192319","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":"O-GlcNAcase transiently translocates to the cytoplasm and regulates osteoblast differentiation","authors":"Xinyu Zheng ,&nbsp;Airi Tanai ,&nbsp;Heriati Sitosari ,&nbsp;Yao Weng ,&nbsp;Anggun Dwi Andini ,&nbsp;Koji Kimura ,&nbsp;Mika Ikegame ,&nbsp;Hirohiko Okamura ,&nbsp;Xiaohua Xie","doi":"10.1016/j.job.2025.100672","DOIUrl":"10.1016/j.job.2025.100672","url":null,"abstract":"<div><h3>Objectives</h3><div>O-GlcNAcylation is a reversible post-translational modification mediated by O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT). Although localization of OGT during differentiation has been well studied, the spatial regulation and role of OGA in the maturation of osteoblasts remains unclear. This study investigated the translocation of OGA and its functional effects during the differentiation of osteoblasts.</div></div><div><h3>Methods</h3><div>Localization of OGA was assessed in mouse calvarial osteoblastic cells using immunohistochemistry and in pre-osteoblastic MC3T3-E1 cells using <em>in vitro</em> staining. OGA-knockout (OGA-KO) MC3T3-E1 cells were generated to evaluate differentiation using the osteogenic markers, Sp7, Dlx5, and Runx2, alkaline phosphatase (ALP) activity, and mineralization stains (von Kossa and Alizarin red).</div></div><div><h3>Results</h3><div>OGA was primarily cytoplasmic in osteoblastic cells of the mouse calvaria. In MC3T3-E1 cells, OGA was translocated from the nucleus to the cytoplasm by differentiation Day 3 and was stabilized by Day 6. OGA-KO cells had enhanced differentiation, increased ALP activity and mineralization, and upregulated Sp7 and Dlx5 expression. Immunohistochemistry showed that Sp7 mirrored the shift in localization of OGA, moving from the nucleus to the cytoplasm by Day 6, whereas Runx2 remained in the nucleus throughout differentiation.</div></div><div><h3>Conclusion</h3><div>Our findings reveal that dynamic translocation of OGA is a key event in early differentiation of osteoblasts that regulates maturation of osteoblasts. These insights suggest a novel regulatory role for OGA and identify potential targets for therapeutic strategies in the regeneration of bone.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 3","pages":"Article 100672"},"PeriodicalIF":2.6,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143922","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":"Vascular inflammation and cancer malignancy","authors":"Yuya Sakurai ,&nbsp;Li Yu ,&nbsp;Aya Matsuda ,&nbsp;Nako Maishi ,&nbsp;Kyoko Hida","doi":"10.1016/j.job.2025.100671","DOIUrl":"10.1016/j.job.2025.100671","url":null,"abstract":"<div><h3>Background</h3><div>Vascular inflammation is a key contributor to cancer progression and metastasis. Tumor endothelial cells (TECs) respond to microbial, metabolic, and therapeutic stimuli by upregulating adhesion molecules and cytokines, which facilitates tumor cell adhesion and immune evasion.</div></div><div><h3>Highlight</h3><div>This review focuses on three representative vascular inflammatory triggers: <em>Streptococcus mutans</em>-induced endothelial activation, the oxLDL/LOX-1 signaling axis, and chemotherapy-induced vascular dysfunction. These mechanisms converge to establish a pre-metastatic niche. Emerging strategies including microbiota modulation, metabolic targeting, and low-dose metronomic (LDM) chemotherapy, have shown promise in preclinical studies for preserving vascular integrity and reducing inflammation.</div></div><div><h3>Conclusion</h3><div>Targeting vascular inflammation is a novel therapeutic approach to suppressing metastasis and cardiovascular events. Further studies are required to validate predictive biomarkers and optimize these strategies for clinical applications.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 2","pages":"Article 100671"},"PeriodicalIF":2.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124125","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":"Genome-wide analyses of susceptibility genes responsible for mandibular prognathism in the Japanese population","authors":"Marie Hoshi-Numahata ,&nbsp;Atsuko Nakanishi-Kimura ,&nbsp;Haruhisa Watanabe ,&nbsp;Mai Nishiura ,&nbsp;Shinnosuke Nishimoto ,&nbsp;Fumi Ueno ,&nbsp;Riyu Koguchi ,&nbsp;Akira Oka ,&nbsp;Yoshiaki Sato ,&nbsp;Takashi S. Kajii ,&nbsp;Tadahiro Iimura","doi":"10.1016/j.job.2025.100670","DOIUrl":"10.1016/j.job.2025.100670","url":null,"abstract":"<div><h3>Background</h3><div>Mandibular prognathism (MP) is a type of malocclusion characterized by an imbalance in the anteroposterior position of the upper and lower jaws. The prevalence of MP in Japan is relatively high, suggesting a unique genetic background in the population.</div></div><div><h3>Highlight</h3><div>Genome-wide analyses identified susceptibility genes responsible for mandibular prognathism in the Japanese population.</div></div><div><h3>Conclusion</h3><div>Identification of the genes associated with malocclusion will pave the way for personalized and precise medicine and contribute to craniofacial biology.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 2","pages":"Article 100670"},"PeriodicalIF":2.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947569","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":"Effects of pro-inflammatory cytokines induced by Porphyromonas gingivalis on cell cycle regulation in brain endothelial cells","authors":"Andrea Fernanda Rodríguez ,&nbsp;Juan Sebastian Buitrago ,&nbsp;Yormaris Castillo ,&nbsp;Gloria Inés Lafaurie ,&nbsp;Diana Marcela Buitrago-Ramirez","doi":"10.1016/j.job.2025.100668","DOIUrl":"10.1016/j.job.2025.100668","url":null,"abstract":"<div><h3>Objectives</h3><div>Advanced periodontitis potentially contributes to Alzheimer's disease (AD) development and progression by altering the blood–brain barrier microenvironment in the cerebral microvascular endothelium. This results, in cytotoxicity, cell cycle disruption, and increased pro-inflammatory cytokine expression, allowing pathogens to enter the brain and damage the central nervous system (CNS). This study evaluated the effects of <em>Porphyromonas gingivalis</em> W83 infection on pro-inflammatory response, cell viability, and cell cycle regulation in mouse brain endothelial cells (mBECs).</div></div><div><h3>Methods</h3><div>mBECs were stimulated with live <em>P. gingivalis</em> at different multiplicity of infection (MOI) values (1:5, 1:10, 1:50, 1:100, 1:200) for 6, 12, 24, and 48 h. Cell viability, cell cycle regulation, and pro-inflammatory cytokine mRNA expression were assessed using the alamarBlue assay, flow cytometry, and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively.</div></div><div><h3>Results</h3><div><em>P. gingivalis</em> reduced cell viability, induced morphological changes in mBECs by &gt;50 % after 48 h (p &lt; 0.05) and caused concentration-dependent arrest in the S and G0/G1 phases of the cell cycle at MOI = 1:100 and 1:200. The <em>Il6</em>, <em>Il1b</em>, and tumor necrosis factor alpha (<em>Tnf</em>) mRNA expression increased significantly compared to that of the controls (p &lt; 0.05).</div></div><div><h3>Conclusions</h3><div><em>P. gingivalis</em> reduced cellular metabolism and induced early cell cycle arrest at the G0/G1 phase in mBECs cells. It also increased the pro-inflammatory response, which could be associated with cell death and possible senescence of brain endothelial cells. These results suggested a possible role for <em>P. gingivalis</em> in the pathogenesis of AD. Further studies are required to elucidate these underlying mechanisms.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 2","pages":"Article 100668"},"PeriodicalIF":2.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912674","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}