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":"2025-12-01","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":"Development of micro-sequestra and associated histological changes in tooth extraction sockets of zoledronate-treated mice","authors":"Gaku Koizumi ,&nbsp;Taku Murata ,&nbsp;Akira Takigawa ,&nbsp;Rina Yamada ,&nbsp;Kasumi Shimizu ,&nbsp;Usagi Hayashi ,&nbsp;Akinobu Hayashi ,&nbsp;Kazuto Kurohara ,&nbsp;Naoya Arai","doi":"10.1016/j.job.2025.100710","DOIUrl":"10.1016/j.job.2025.100710","url":null,"abstract":"<div><h3>Objectives</h3><div>Administration of bisphosphonates to mice do not always impair healing after tooth extraction. However, it is unclear whether there are any histological differences between the macroscopically healed extraction sockets of bisphosphonate- and saline-injected mice.</div></div><div><h3>Methods</h3><div>Mice received a single intravenous injection of 540 μg/kg zoledronic acid or saline, and the maxillary first molars were extracted one week later. Healing of the extraction sockets was examined histologically and by micro-computed tomography.</div></div><div><h3>Results</h3><div>Zoledronic acid and saline did not impair gross wound healing. Microscopically, the soft and the hard tissues of the extraction sockets were completely regenerated two weeks post-extraction. However, there were small bone fragments that varied from 10 μm to 200 μm in size in the connective tissues of the oral mucosa in the zoledronic acid-treated mice. The bone fragments had empty osteocyte lacunae, indicating that they were micro-sequestra. There was recruitment of multinucleated giant cells and contact of pseudoepitheliomatous hyperplasia in association with the bone fragments. These features were not present four weeks post-extraction.</div></div><div><h3>Conclusions</h3><div>This study demonstrated that there were micro-sequestra in tooth extraction sockets after zoledronic acid treatment, even if there was no osteonecrosis or bone exposure. Although the significance of bone fragments and the associated changes is unclear, these findings may assist in understanding the sub-clinical state of adverse effects induced by bisphosphonates.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100710"},"PeriodicalIF":2.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525850","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":"Sex determination and age estimation method using the trabecular structure of the third cervical vertebral body by head and neck CT in Japanese adults","authors":"Akihiro Ochiai ,&nbsp;Atsushi Iwawaki ,&nbsp;Yusei Otaka ,&nbsp;Takeru Ishii ,&nbsp;Kota Ozawa ,&nbsp;Yuko Otomo ,&nbsp;Shinji Kito ,&nbsp;Hideki Saka","doi":"10.1016/j.job.2025.100685","DOIUrl":"10.1016/j.job.2025.100685","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to develop sex determination and age estimation equations using the trabecular structure of the third cervical vertebra from head and neck computed tomography (CT) images by analyzing bone microarchitecture.</div></div><div><h3>Methods</h3><div>Trabecular bone structure was analyzed in a centrally located region of interest (ROI) within the third cervical vertebral body (C3) using CT scans from 132 Japanese adults (66 males and 66 females). Three primary measurements were taken: total vertebral volume (Tissue Volume, TV; mm³), trabecular bone volume (Bone Volume, BV; mm³), and trabecular bone surface area (Bone Surface, BS; mm²). Bone volume fraction (BV/TV; %) was calculated as a bone density index. Additional parameters—bone surface-to-volume ratio (BS/TV; mm²/mm³), bone surface-to-bone volume ratio (BS/BV; mm²/mm³), trabecular thickness (Tb.Th; μm), and trabecular number (Tb.N; 1/mm)—were measured. Sex differences were evaluated, and a logistic regression model was developed for sex determination. Age estimation equations were created for the total sample and by sex.</div></div><div><h3>Results</h3><div>Males had larger TV, BV, and BS than females. The sex determination model achieved 80.0 % accuracy. BV/TV declined with age, especially in females, while TV showed an increasing trend in males. Age estimation was more accurate for females (mean absolute error [MAE]: 11.67 years) than that for males (MAE: 14.15 years). Sex-related differences reflect skeletal variation and suggest menopause-associated bone loss may explain female model performance.</div></div><div><h3>Conclusions</h3><div>C3 trabecular structure offers forensic potential for both sex and age prediction. The developed models may contribute to individual identification by providing biologically meaningful estimations.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 3","pages":"Article 100685"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779505","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":"Analysis of the distribution of HEV by immunohistochemistry using a mouse oral squamous cell carcinoma model","authors":"Zixiao Ren ,&nbsp;Aya Matsuda ,&nbsp;Nako Maishi ,&nbsp;Yasuhiro Hida ,&nbsp;Takashi Niiyama ,&nbsp;Li Yu ,&nbsp;Weihan Sun ,&nbsp;Yoichi Ohiro ,&nbsp;Kyoko Hida","doi":"10.1016/j.job.2025.100684","DOIUrl":"10.1016/j.job.2025.100684","url":null,"abstract":"<div><h3>Objective</h3><div>The density of tumor-associated high endothelial venule (TA-HEV) correlates with a favorable prognosis in various tumors, including oral squamous cell carcinoma (OSCC). Despite the association of TA-HEVs with a better prognosis, their changes during tumor progression remain unclear. Therefore, this study aimed to examine these alterations in a mouse OSCC model.</div></div><div><h3>Methods</h3><div>Mice were treated with water containing 4NQO to establish a mouse OSCC model. Immunohistochemical analyses were performed using CD31 and MECA 79 antibodies to evaluate TA-HEV alterations during tumor progression.</div></div><div><h3>Results</h3><div>Tongue samples were histologically classified into untreated, normal, dysplasia, and carcinoma groups. During the dysplastic stage, the number of blood vessels increased, and pericyte coverage was reduced as the carcinoma developed. Moreover, HEVs were more abundant in the dysplasia and carcinoma groups, with an increased number of HEVs infiltrated with CD8⁺ T cells as the lesion progressed. The location and morphology of the HEVs changed during the transition from normal tissue to carcinoma, with the distribution of the TA-HEVs associated with the tumor growth patterns. Specifically, TA-HEVs were frequently found within the tumor in endophytic carcinomas, and at the tumor margins in exophytic carcinomas. Margin TA-HEVs correlated with a higher number of T cells than HEVs within the tumors.</div></div><div><h3>Conclusion</h3><div>OSCC-associated HEVs increase in density with tumor progression, and margin TA-HEVs suggests a better anti-tumor prognosis compared with intra-TA-HEVs.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 3","pages":"Article 100684"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749609","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 anti-RANKL and anti-PD-1 antibodies on cancer-induced osteolysis in mice","authors":"Po-Chin Chao ,&nbsp;Akiko Karakawa ,&nbsp;Masahiro Hosonuma ,&nbsp;Yuki Azetsu ,&nbsp;Shogo Kamikawa ,&nbsp;Aoi Oshio ,&nbsp;Masahiro Chatani ,&nbsp;Tatsuo Shirota ,&nbsp;Masamichi Takami","doi":"10.1016/j.job.2025.100682","DOIUrl":"10.1016/j.job.2025.100682","url":null,"abstract":"<div><h3>Objectives</h3><div>Denosumab, an anti-bone resorptive agent composed of the anti-receptor activator of nuclear factor-κB ligand (RANKL) monoclonal antibody, and nivolumab, an immune checkpoint inhibitor composed of the anti-programmed death-1 (PD-1) antibody, are administered to suppress cancer growth. The present study examined the effects of the administration of anti-RANKL antibody alone and in combination with anti-PD-1 antibody on cancer-induced osteolysis in mice.</div></div><div><h3>Methods</h3><div>Cells from the mouse breast cancer cell line, 4T1, were injected into the subperiosteal region of mice calvariae, and anti-RANKL antibodies, with or without anti-PD-1 antibodies, were administered. From 0 to 15 days, tumor volume, osteolysis area, and osteoclast distribution were analyzed.</div></div><div><h3>Results</h3><div>Tumor volume and osteolysis area in the calvariae increased with time and the number of 4T1 cells injected. Administration of anti-RANKL antibody inhibited cancer-induced osteoclast formation and osteolysis but did not suppress tumor growth. Furthermore, the administration of anti-PD-1 antibody, with or without a low dose of anti-RANKL antibody, did not suppress tumor growth or osteolysis. However, an increase in osteoclast-like cells was found, not only in the calvariae, but also in cancer tissues that received anti-PD-1 antibody.</div></div><div><h3>Conclusions</h3><div>Inhibition of RANKL function by the anti-RANKL antibody did not affect tumor growth, although it suppressed osteolysis. Interestingly, the anti-PD-1 antibody induced osteoclast-like cells at the tumor sites. Thus, it is postulated that low-dose anti-RANKL and anti-PD-1 antibodies do not have synergistic effects on osteolysis, whereas anti-PD-1 antibody induces the formation of osteoclasts the treated tumor sites.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 3","pages":"Article 100682"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704835","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":"2025-09-01","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":"2025-09-01","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":"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":"2025-09-01","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":"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":"2025-09-01","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":"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":"2025-09-01","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}