Journal of Oral Biosciences最新文献

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Complement components C1r and C1s promote oral squamous cell carcinoma cell proliferation 补体成分C1r和C1s促进口腔鳞状细胞癌细胞增殖
IF 2.3
Journal of Oral Biosciences Pub Date : 2025-08-19 DOI: 10.1016/j.job.2025.100691
Thinh Thi Kim Truong , Tatsufumi Fujimoto , Shinsuke Fujii , Kari J. Kurppa , Kana Hasegawa , Yudai Tajiri , Masafumi Moriyama , Tamotsu Kiyoshima
{"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}
引用次数: 0
Inhibition of Gremlin1 reduces osteoclast activation and alleviates inflammation-induced bone loss by disrupting the NF-κB signaling pathway 抑制Gremlin1可通过破坏NF-κB信号通路降低破骨细胞活化,减轻炎症诱导的骨质流失
IF 2.3
Journal of Oral Biosciences Pub Date : 2025-08-19 DOI: 10.1016/j.job.2025.100686
Yuting Wang , Wenlan Li , Yifei Tang , Wenli Mu , Mingfei Wang , Wenjing Liu , Xiaomei Guo , Tiezhou Hou , Xiaoyue Guan
{"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}
引用次数: 0
Spermidine enhances Immunoglobulin A secretory capacity in rat salivary glands: An ex vivo study 亚精胺增强大鼠唾液腺免疫球蛋白A分泌能力的离体研究
IF 2.3
Journal of Oral Biosciences Pub Date : 2025-08-13 DOI: 10.1016/j.job.2025.100687
Yuta Hosomi , Yuko Yamamoto , Ryuta Endo , Masahiro Sugimoto , Wakako Sakaguchi , Shinya Fuchida , Toshiya Morozumi , Juri Saruta , Keiichi Tsukinoki
{"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}
引用次数: 0
Senescence in palatal rugae development 腭纹发育中的衰老
IF 2.3
Journal of Oral Biosciences Pub Date : 2025-08-12 DOI: 10.1016/j.job.2025.100688
Finsa Tisna Sari , Maiko Kawasaki , Katsushige Kawasaki , Vanessa Utama , Alex Kesuma , Makoto Fukushima , Takehisa Kudo , Akira Fujita , Kaya Ichikawa , Yurie Sato-Yamada , Ippei Shimizu , Tohru Minamino , Jun Nihara , Atsushi Ohazama
{"title":"Senescence in palatal rugae development","authors":"Finsa Tisna Sari ,&nbsp;Maiko Kawasaki ,&nbsp;Katsushige Kawasaki ,&nbsp;Vanessa Utama ,&nbsp;Alex Kesuma ,&nbsp;Makoto Fukushima ,&nbsp;Takehisa Kudo ,&nbsp;Akira Fujita ,&nbsp;Kaya Ichikawa ,&nbsp;Yurie Sato-Yamada ,&nbsp;Ippei Shimizu ,&nbsp;Tohru Minamino ,&nbsp;Jun Nihara ,&nbsp;Atsushi Ohazama","doi":"10.1016/j.job.2025.100688","DOIUrl":"10.1016/j.job.2025.100688","url":null,"abstract":"<div><h3>Objectives</h3><div>Periodic patterning is a common feature observed in many organs and is believed to share common molecular mechanisms during development. Palatal rugae, periodically patterned ridges located on the mammalian hard palate, provide an excellent experimental model for investigating the mechanisms of periodic patterning.</div></div><div><h3>Methods</h3><div>We investigated senescence during palatal rugae development in wild-type mice.</div></div><div><h3>Results</h3><div>Senescence-associated β-galactosidase (SA-β-gal) activity was observed during palatal rugae development in wild-type mice. During embryonic days (E) 12–14, SA-β-gal activity was detected in the placodes of rugae 1–4 and 8. IL-6 and p21 expression were present in the placodes of these rugae at these stages. SA-β-gal signal began to disappear at E15 and was no longer detectable in all rugae at E16. The expression of macrophage markers was observed as SA-β-gal activity disappeared. SA-β-gal activity persisted in mice with epithelial conditional deletion of <em>p21</em>. Furthermore, we successfully reduced SA-β-gal activity using a senolytic drug.</div></div><div><h3>Conclusions</h3><div>Senescence-like cells, activated via a p21-independent pathway, are present during palatal rugae development.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100688"},"PeriodicalIF":2.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144826412","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}
引用次数: 0
Hyperglycemia in obese type 2 diabetes mellitus rats affects pulp wound healing 肥胖2型糖尿病大鼠高血糖影响牙髓创面愈合
IF 2.3
Journal of Oral Biosciences Pub Date : 2025-08-09 DOI: 10.1016/j.job.2025.100683
Rosa Baldeon-Gutierrez , Naoto Ohkura , Nagako Yoshiba , Shintaro Takahara , Susan Gomez-Kasimoto , Takako Ida , Naoki Edanami , Kunihiko Yoshiba , Shoji Takenaka , Yuichiro Noiri
{"title":"Hyperglycemia in obese type 2 diabetes mellitus rats affects pulp wound healing","authors":"Rosa Baldeon-Gutierrez ,&nbsp;Naoto Ohkura ,&nbsp;Nagako Yoshiba ,&nbsp;Shintaro Takahara ,&nbsp;Susan Gomez-Kasimoto ,&nbsp;Takako Ida ,&nbsp;Naoki Edanami ,&nbsp;Kunihiko Yoshiba ,&nbsp;Shoji Takenaka ,&nbsp;Yuichiro Noiri","doi":"10.1016/j.job.2025.100683","DOIUrl":"10.1016/j.job.2025.100683","url":null,"abstract":"<div><h3>Objective</h3><div>Hyperglycemia in individuals with type 2 diabetes mellitus is associated with delayed wound healing, although the underlying mechanism remains unclear. Macrophages play a crucial role in the initiation, maintenance, and resolution of inflammation by polarizing into proinflammatory and anti-inflammatory subtypes. Hyperglycemia may interfere with odontoblast-like cell differentiation and cause persistent proinflammatory polarization in individuals with type 2 diabetes mellitus.</div></div><div><h3>Methods</h3><div>Eight-week-old spontaneously diabetic Torii fatty rats (model rats for type 2 diabetes mellitus) and Sprague-Dawley rats (control group, four rats per group) were used. The upper left first molars underwent pulpotomy and were capped with mineral trioxide aggregates for observation after seven days. Osteopontin expression was analyzed to assess the initiation of wound healing. Immunofluorescence analysis of nestin and alpha-smooth muscle actin was used to evaluate odontoblast-like cell differentiation. Double-positive cells among proinflammatory and anti-inflammatory macrophages were counted. Furthermore, the proliferating cell nuclear antigen (PCNA), Thy1, and CD146 were evaluated to assess cell proliferation and mesenchymal stem cells.</div></div><div><h3>Results</h3><div>Inflammation persisted in the model rats, and no reparative dentin was formed. Macrophages in the model rats showed an increased proinflammatory response and a reduced anti-inflammatory response.</div></div><div><h3>Conclusion</h3><div>Hyperglycemia interferes with macrophage polarization and odontoblast-like cell differentiation, thus impairing wound healing in this model.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100683"},"PeriodicalIF":2.3,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842233","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}
引用次数: 0
Sex determination and age estimation method using the trabecular structure of the third cervical vertebral body by head and neck CT in Japanese adults 利用日本成人头颈部CT第三颈椎小梁结构的性别测定和年龄估计方法
IF 2.3
Journal of Oral Biosciences Pub Date : 2025-08-06 DOI: 10.1016/j.job.2025.100685
Akihiro Ochiai , Atsushi Iwawaki , Yusei Otaka , Takeru Ishii , Kota Ozawa , Yuko Otomo , Shinji Kito , Hideki Saka
{"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; mm<sup>3</sup>), trabecular bone volume (Bone Volume, BV; mm<sup>3</sup>), and trabecular bone surface area (Bone Surface, BS; mm<sup>2</sup>). Bone volume fraction (BV/TV; %) was calculated as a bone density index. Additional parameters—bone surface-to-volume ratio (BS/TV; mm<sup>2</sup>/mm<sup>3</sup>), bone surface-to-bone volume ratio (BS/BV; mm<sup>2</sup>/mm<sup>3</sup>), 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":"2025-08-06","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}
引用次数: 0
Analysis of the distribution of HEV by immunohistochemistry using a mouse oral squamous cell carcinoma model 利用小鼠口腔鳞状细胞癌模型免疫组织化学方法分析HEV的分布
IF 2.3
Journal of Oral Biosciences Pub Date : 2025-07-31 DOI: 10.1016/j.job.2025.100684
Zixiao Ren , Aya Matsuda , Nako Maishi , Yasuhiro Hida , Takashi Niiyama , Li Yu , Weihan Sun , Yoichi Ohiro , Kyoko Hida
{"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<sup>+</sup> 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":"2025-07-31","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}
引用次数: 0
Effects of anti-RANKL and anti-PD-1 antibodies on cancer-induced osteolysis in mice 抗rankl和抗pd -1抗体对小鼠肿瘤性骨溶解的影响
IF 2.6
Journal of Oral Biosciences Pub Date : 2025-07-26 DOI: 10.1016/j.job.2025.100682
Po-Chin Chao , Akiko Karakawa , Masahiro Hosonuma , Yuki Azetsu , Shogo Kamikawa , Aoi Oshio , Masahiro Chatani , Tatsuo Shirota , Masamichi Takami
{"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":"2025-07-26","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}
引用次数: 0
Intentionally perforating the pulp chamber floor promotes M2 macrophage polarization in the dental pulp following tooth replantation in mice 在小鼠牙齿再植后,有意在牙髓室底穿孔可促进牙髓中M2巨噬细胞的极化
IF 2.6
Journal of Oral Biosciences Pub Date : 2025-07-18 DOI: 10.1016/j.job.2025.100681
Hiroto Sano , Kuniko Nakakura-Ohshima , Angela Quispe-Salcedo , Yasuo Okada , Takuichi Sato , Hayato Ohshima
{"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}
引用次数: 0
The unique molecular signature of TMJ as compared to the knee, demonstrates its susceptibility to osteoarthritis 与膝关节相比,TMJ独特的分子特征表明其对骨关节炎的易感性
IF 2.6
Journal of Oral Biosciences Pub Date : 2025-07-15 DOI: 10.1016/j.job.2025.100680
Rajnikant Dilip Raut , Chumki Choudhury , Amit Kumar Chakraborty , Harpreet Singh , Pushkar Mehra , Louis Gerstenfeld , Alejandro Almarza , Manish V. Bais
{"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}
引用次数: 0
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