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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 Q1 DENTISTRY, ORAL SURGERY & MEDICINE 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

Objectives

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.

Methods

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.

Results

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 (Mmp13, Postn, and Col1a1) 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 in vitro 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.

Conclusions

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.
目的骨关节炎(OA)是一种使人衰弱的关节疾病,影响全世界数百万人,主要影响颞下颌关节(TMJs)和膝关节。尽管其普遍存在,TMJ-OA仍未得到充分研究。本研究比较了TMJ与膝关节的转录特征,并探讨了TMJ- oa内侧和表面层的转录差异。方法采集6月龄C57BL/ 6j小鼠的stmj和膝关节组织标本。收集山羊TMJ浅层和内层软骨,分离后用白细胞介素-1β处理。所有样本都进行了大量RNA测序,随后进行了差异表达和基因集富集分析。结果共鉴定出4031个蛋白编码基因在TMJ与膝关节中差异表达,其中神经元系统基因显著富集,先天免疫系统基因富集程度较低。关键的OA生物标志物(Mmp13、Postn和Col1a1)在TMJ中的表达更高,表明OA的易感性更高。IL-1β处理山羊TMJ软骨细胞模拟了天然TMJ- oa样的转录变化和免疫反应,这在兔TMJ- oa模型中也观察到了。这些结果验证了山羊TMJ-OA体外模型的有效性。il -1β处理的山羊TMJ内侧软骨层富含oa相关转录因子、衰老基因和表观遗传调控因子。结论:本研究表明,与膝关节相比,TMJ具有独特的转录组特征,确定了OA和疼痛相关基因的不同易感性。这些发现为TMJ-OA的分子机制和治疗靶点选择提供了有价值的见解。
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引用次数: 0
Complete genome sequence of a tetracycline-resistant Streptococcus mutans strain carrying the tet(M) gene 携带tet(M)基因的四环素耐药突变链球菌株的全基因组序列。
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-20 DOI: 10.1016/j.job.2025.100679
Saki Nishihama , Yujin Suzuki , Tomoaki Shintani , Manami Tsunoi , Junzo Hisatsune , Yo Sugawara , Katsuhiro Takeda , Miki Kawada-Matsuo , Mikihito Kajiya , Motoyuki Sugai , Hideki Shiba , Hitoshi Komatsuzawa

Introduction

Tetracyclines are widely used in dental treatment. Here, we report the genomic information of the tetracycline-resistant Streptococcus mutans strain, HSM45, for the first time.

Methods

Susceptibility to tetracycline was determined using the microdilution method. The complete genome sequence of HSM45 was determined and compared with public genome data.

Results

HSM45 was resistant to tetracycline. The tetracycline resistance gene tet(M) was carried by Tn916, a conjugative transposon that is widely found in Gram-positive bacteria.

Conclusion

This study showed that S. mutans can acquire tetracycline resistance and it can also be a source of horizontal transfer of resistance genes.
四环素类药物在牙科治疗中应用广泛。在此,我们首次报道了四环素耐药突变链球菌HSM45的基因组信息。方法:采用微量稀释法测定对四环素的药敏。测定HSM45的全基因组序列,并与公开的基因组数据进行比较。结果:HSM45对四环素耐药。四环素耐药基因tet(M)由一种广泛存在于革兰氏阳性菌中的共轭转座子Tn916携带。结论:本研究表明变形链球菌可以获得四环素耐药性,也可能是抗性基因水平转移的来源。
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引用次数: 0
Identification of a transposon variant of Porphyromonas gingivalis expressing long Mfa1 fimbriae due to mfa2 inactivation 由于mfa2失活,牙龈卟啉单胞菌表达长Mfa1菌膜的转座子变异的鉴定。
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-18 DOI: 10.1016/j.job.2025.100677
Naoyoshi Miwa , Miyuna Fujimoto , Kotaro Sakae , Tomohiko Iwase , Makoto Hirohata , Yoshikazu Naiki , Kiyoshi Nishikawa , Hiroyuki Nawa , Yoshiaki Hasegawa

Objectives

Fimbriae expressed by Porphyromonas gingivalis, 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—mfa170A, mfa170B, and mfa153—based on gene sequence. Although strain D83T3 is classified as mfa170A, like ATCC 33277, it expresses a 73 kDa Mfa1. This study aimed to investigate D83T3's unique functional properties to improve mfa1 genotyping.

Methods

The fimA-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 mfa1 was sequenced. Mfa2 expression and the presence of Mfa3–5, putative tip proteins in the fimbriae, were confirmed by immunoblotting.

Results

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 mfa1 and mfa2 at D83T3. Mfa2 expression was reduced in D83T3 cells, and Mfa3–5 was absent from the fimbriae.

Conclusions

D83T3 is a transposon insertion variant that releases abnormally long Mfa1 fimbriae extracellularly due to mfa2 inactivation. Our study's findings offer new insights, and analysis of the mfa1-mfa2 gene structure can complement mfa1 genotyping for the classification of P. gingivalis.
目的:牙周病原菌牙龈卟啉单胞菌表达的菌毛在生物膜的形成中起关键作用。在ATCC 33277型菌株中,Mfa1毛被Mfa2固定在细胞表面形成短结构,Mfa2是一种参与毛长度调节的外膜蛋白。Mfa1是主要的纤原蛋白,根据基因序列可分为mfa170a、mfa170B和mfa153三种基因型。虽然菌株D83T3与ATCC 33277一样被归类为mfa170A,但它表达一个73 kDa的Mfa1。本研究旨在研究D83T3的独特功能特性,以改善mfa1基因分型。方法:以fima缺失株ATCC 33277 (JI-1)为对照。免疫印迹法分析Mfa1的聚合和定位。用Edman降解法评价n端加工过程。透射电镜观察毛层形态。对mfa1下游区域进行测序。Mfa2和Mfa3-5的表达通过免疫印迹法证实。结果:D83T3培养上清液中主要检测到73 kDa的Mfa1聚合物。在牙龈痛识别位点确认了卵裂。D83T3的Mfa1菌毛比JI-1的长。在D83T3的mfa1和mfa2之间观察到IS5转座酶插入。Mfa2在D83T3细胞中表达降低,Mfa3-5在菌毛中缺失。结论:D83T3是一种转座子插入变异,由于mfa2失活,在细胞外释放异常长的Mfa1菌膜。我们的研究结果提供了新的见解,分析mfa1-mfa2基因结构可以补充mfa1基因分型对牙龈假单胞菌的分类。
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引用次数: 0
Proteolytic N-terminal processing of Mfa proteins in the periodontal pathogen Porphyromonas gingivalis 牙周病原菌牙龈卟啉单胞菌Mfa蛋白的蛋白水解n端加工。
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-13 DOI: 10.1016/j.job.2025.100678
Makoto Hirohata , Yoshikazu Naiki , Akihiro Oishi , Kiyoshi Nishikawa , Richard J. Lamont , Karina Persson , Yoshiaki Hasegawa

Objectives

The asaccharolytic bacterium Porphyromonas gingivalis 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.

Methods

Missense mutations were introduced in the N-terminal regions of mfa1 and mfa4 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.

Results

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.

Conclusion

These results suggest the existence of a compensatory proteolytic network in P. gingivalis and emphasize the biological importance of post-translational modifications in fimbrial assembly.
目的:解糖菌牙龈卟啉单胞菌通过Mfa1菌膜调节生物膜的形成,Mfa1菌膜由主要亚基Mfa1和包括推测的尖端粘附素Mfa4在内的辅助蛋白组成。这些成分通过牙龈痛的n端前导肽裂解而成熟。然而,控制毛层组装的机制仍不清楚。本研究考察了蛋白酶依赖的n端加工在毛毛生物发生过程中Mfa1和Mfa4的成熟和结合中的作用。方法:用丙氨酸取代RgpA/B和kgp特异性切割位点,在mfa1和mfa4的n端区域引入错义突变。ELISA法分析突变细胞中Mfa1的表面表达。通过离子交换色谱法从亲本菌株和突变菌株中纯化Mfa1菌毛,测定Mfa1和Mfa4的n端序列。针对Mfa4先导肽的抗体用于定位研究。结果:尽管在RgpA/B切割位点上有丙氨酸取代,但Mfa1加工仍然存在,表明Kgp或其他酶(如二肽基肽酶)进行了代偿性切割。成熟的Mfa1被运输到细胞表面,并被纳入毛中。仅在菌毛中检测到成熟形式的Mfa4,而内膜中富集了先导肽。结论:这些结果表明牙龈假单胞菌中存在代偿性蛋白水解网络,并强调了翻译后修饰在菌毛组装中的生物学重要性。
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引用次数: 0
Repetitive/rhythmic masticatory muscle activity under urethane anesthesia in guinea pigs: a descriptive pilot study 氨基甲酸乙酯麻醉下豚鼠咀嚼肌的重复性/节律性活动:一项描述性的初步研究。
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-05-30 DOI: 10.1016/j.job.2025.100673
Sho Katsura , Yutaka Matsuura , Ayano Katagiri , Hiroki Toyoda , Makoto Higashiyama , Yuji Masuda , Takafumi Kato

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.
目的:有节奏/重复的咀嚼肌活动可能在无意识大脑状态(如睡眠)的循环交替中自发发生。需要一个实验模型来阐明这些潜在的机制。本研究研究了氨基甲酸乙酯麻醉下循环状态交替时颌部运动和咀嚼肌活动。方法:7只雄性豚鼠(420 ~ 594 g)麻醉后,同时记录皮质脑电图、心电图、鼻气流及颌部运动和颌肌肌电活动。根据脑电图(EEG)的δ和θ功率将大脑皮层状态分为失活状态和激活状态。在两种皮质状态下测量呼吸和心率。视觉上对节律性下颌运动(RJMs)进行评分,并分析咀嚼肌电图爆发的特征。分析了皮质、心脏和呼吸活动的短暂变化与RJMs的关系。结果:皮层活动、呼吸和心率在激活状态和失活状态之间存在显著差异。在321例RJMs中,有290例发生在聚氨酯麻醉下;大多数(73.7%)在激活状态下被评分。RJM发作与交替侧颌偏移有关,主要是咬肌激活,偶尔伴有磨牙声。RJMs发生前,脑电图δ活动减少,心脏和呼吸活动短暂性增加。结论:在氨基甲酸乙酯麻醉下,咀嚼肌可能在脑状态的循环交替中被重复和有节奏地激活。用聚氨酯麻醉的豚鼠是一种潜在的实验模型,用于研究无意识状态(如睡眠磨牙症)下RJMs产生的机制。
{"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}
引用次数: 0
O-GlcNAcase transiently translocates to the cytoplasm and regulates osteoblast differentiation O-GlcNAcase可瞬时易位至细胞质并调节成骨细胞的分化。
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-05-22 DOI: 10.1016/j.job.2025.100672
Xinyu Zheng , Airi Tanai , Heriati Sitosari , Yao Weng , Anggun Dwi Andini , Koji Kimura , Mika Ikegame , Hirohiko Okamura , Xiaohua Xie

Objectives

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.

Methods

Localization of OGA was assessed in mouse calvarial osteoblastic cells using immunohistochemistry and in pre-osteoblastic MC3T3-E1 cells using in vitro 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).

Results

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.

Conclusion

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.
目的:o - glcn酰化是由O-GlcNAcase (OGA)和o - glcnnac transferase (OGT)介导的一种可逆的翻译后修饰。虽然OGT在分化过程中的定位已经得到了很好的研究,但OGA在成骨细胞成熟过程中的空间调节和作用尚不清楚。本研究探讨了成骨细胞分化过程中OGA的易位及其功能作用。方法:采用免疫组化法测定小鼠颅骨成骨细胞中OGA的定位,体外染色法测定成骨前MC3T3-E1细胞中的OGA定位。生成oga敲除(OGA-KO) MC3T3-E1细胞,利用成骨标志物Sp7、Dlx5和Runx2、碱性磷酸酶(ALP)活性和矿化染色(von Kossa和茜素红)评估分化情况。结果:OGA主要存在于小鼠颅骨成骨细胞的细胞质中。在MC3T3-E1细胞中,OGA在分化第3天从细胞核转移到细胞质,并在第6天稳定下来。OGA-KO细胞分化增强,ALP活性和矿化增加,Sp7和Dlx5表达上调。免疫组化显示Sp7反映了OGA的定位变化,在第6天从细胞核转移到细胞质,而Runx2在整个分化过程中都留在细胞核中。结论:OGA的动态易位是成骨细胞早期分化调控成骨细胞成熟的关键事件。这些见解表明了OGA的一种新的调节作用,并确定了骨再生治疗策略的潜在靶点。
{"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}
引用次数: 0
Vascular inflammation and cancer malignancy 血管炎症和恶性肿瘤
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-05-20 DOI: 10.1016/j.job.2025.100671
Yuya Sakurai , Li Yu , Aya Matsuda , Nako Maishi , Kyoko Hida

Background

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.

Highlight

This review focuses on three representative vascular inflammatory triggers: Streptococcus mutans-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.

Conclusion

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.
背景:血管炎症是癌症进展和转移的关键因素。肿瘤内皮细胞(tec)通过上调粘附分子和细胞因子对微生物、代谢和治疗刺激做出反应,从而促进肿瘤细胞的粘附和免疫逃逸。本文综述了三种具有代表性的血管炎症触发因素:变形链球菌诱导的内皮激活、oxLDL/LOX-1信号轴和化疗诱导的血管功能障碍。这些机制共同建立了转移前生态位。包括微生物群调节、代谢靶向和低剂量节律化疗在内的新兴策略在临床前研究中显示出保持血管完整性和减少炎症的希望。结论靶向血管炎症是抑制血管转移和心血管事件的新途径。需要进一步的研究来验证预测性生物标志物并优化这些策略以用于临床应用。
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引用次数: 0
Genome-wide analyses of susceptibility genes responsible for mandibular prognathism in the Japanese population 日本人群下颌前突易感基因的全基因组分析
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-05-09 DOI: 10.1016/j.job.2025.100670
Marie Hoshi-Numahata , Atsuko Nakanishi-Kimura , Haruhisa Watanabe , Mai Nishiura , Shinnosuke Nishimoto , Fumi Ueno , Riyu Koguchi , Akira Oka , Yoshiaki Sato , Takashi S. Kajii , Tadahiro Iimura

Background

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.

Highlight

Genome-wide analyses identified susceptibility genes responsible for mandibular prognathism in the Japanese population.

Conclusion

Identification of the genes associated with malocclusion will pave the way for personalized and precise medicine and contribute to craniofacial biology.
背景:下颌前突症(MP)是一种以上下颌骨前后位置不平衡为特征的错颌畸形。MP在日本的患病率相对较高,表明在人群中有独特的遗传背景。亮点:全基因组分析确定了日本人群下颌前伸症的易感基因。结论错颌畸形相关基因的鉴定将为个性化、精准化治疗铺平道路,并有助于颅面生物学的研究。
{"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}
引用次数: 0
Effects of pro-inflammatory cytokines induced by Porphyromonas gingivalis on cell cycle regulation in brain endothelial cells 牙龈卟啉单胞菌诱导的促炎细胞因子对脑内皮细胞周期调控的影响
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-05-02 DOI: 10.1016/j.job.2025.100668
Andrea Fernanda Rodríguez , Juan Sebastian Buitrago , Yormaris Castillo , Gloria Inés Lafaurie , Diana Marcela Buitrago-Ramirez

Objectives

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 Porphyromonas gingivalis W83 infection on pro-inflammatory response, cell viability, and cell cycle regulation in mouse brain endothelial cells (mBECs).

Methods

mBECs were stimulated with live P. gingivalis 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.

Results

P. gingivalis reduced cell viability, induced morphological changes in mBECs by >50 % after 48 h (p < 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 Il6, Il1b, and tumor necrosis factor alpha (Tnf) mRNA expression increased significantly compared to that of the controls (p < 0.05).

Conclusions

P. gingivalis 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 P. gingivalis in the pathogenesis of AD. Further studies are required to elucidate these underlying mechanisms.
目的:晚期牙周炎可能通过改变大脑微血管内皮的血脑屏障微环境而促进阿尔茨海默病(AD)的发生和进展。这导致细胞毒性、细胞周期中断和促炎细胞因子表达增加,使病原体进入大脑并损害中枢神经系统(CNS)。本研究评估了牙龈卟啉单胞菌W83感染对小鼠脑内皮细胞(mBECs)的促炎反应、细胞活力和细胞周期调节的影响。方法采用不同感染倍数(MOI)值(1:5、1:10、1:50、1:100、1:200)的活牙龈假单胞菌刺激smbecs 6、12、24和48 h,分别采用alamarBlue法、流式细胞术和逆转录定量聚合酶链反应(RT-qPCR)检测细胞活力、细胞周期调节和促炎细胞因子mRNA表达。48 h后,牙龈炎降低细胞活力,诱导mBECs形态学改变50% (p <;0.05),并在MOI = 1:100和1:200时在细胞周期的S期和G0/G1期引起浓度依赖性阻滞。与对照组相比,il - 6、il - 1b和肿瘤坏死因子α (Tnf) mRNA的表达显著升高(p <;0.05) .ConclusionsP。牙龈炎降低mBECs细胞的细胞代谢,诱导细胞周期早期阻滞在G0/G1期。它还增加了促炎反应,这可能与细胞死亡和可能的脑内皮细胞衰老有关。这些结果提示牙龈假单胞菌可能在AD的发病机制中起作用。需要进一步的研究来阐明这些潜在的机制。
{"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}
引用次数: 0
Efficacy of electrical stimulation for antimicrobial capacity of titanium materials implants: A systematic review and meta-analysis 电刺激对钛材料植入物抗菌能力的影响:一项系统综述和荟萃分析
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-04-30 DOI: 10.1016/j.job.2025.100669
Simone Kreve, Andréa C. dos Reis

Background

Antimicrobial resistance undermines the effectiveness of drugs for treating implant-associated infections. Consequently, there is growing interest in identifying alternative methods to prevent and eliminate infections. The aim of this systematic review was to ascertain whether the electrical stimulation of titanium implants or titanium-based implant materials has antimicrobial properties against bacterial biofilms. The search was conducted in various databases, including PubMed/Medline, Web of Science, EMBASE, SCOPUS, and Google Scholar, in February 2024. In addition, a manual search of the reference lists of the included articles was conducted. The eligibility criteria included in vivo and in vitro studies evaluating the effects of electrical stimulation on titanium implants or titanium-based implant materials in reducing biofilm formation or adhesion as well as eradicating or reducing the viability of bacterial biofilms. The variability between studies was determined using the inverse variance method with random- and fixed-effects models. Heterogeneity was assessed using the I2 and prediction interval statistics. Publication bias was qualitatively evaluated using funnel plots.

Highlights

Different electrical stimulation (ES) parameters (current and voltage) exhibited antibacterial activity, resulting in either bacteriostatic or bactericidal effects.

Conclusions

ES in titanium or titanium-based implant materials confers antimicrobial capacity against bacterial biofilms, and its effectiveness depends on the applied tension. The association between ES and antimicrobials was more robust than with ES administered individually.
抗生素耐药性破坏了治疗种植体相关感染药物的有效性。因此,人们对确定预防和消除感染的替代方法越来越感兴趣。本系统综述的目的是确定钛植入物或钛基植入物材料的电刺激是否对细菌生物膜具有抗菌性能。检索于2024年2月在PubMed/Medline、Web of Science、EMBASE、SCOPUS和谷歌Scholar等多个数据库中进行。此外,还进行了人工检索纳入文章的参考文献列表。资格标准包括体内和体外研究,评估电刺激对钛植入物或钛基植入材料在减少生物膜形成或粘附以及根除或降低细菌生物膜活力方面的影响。研究之间的可变性是用随机效应和固定效应模型的反方差法确定的。异质性评估采用I2和预测区间统计。发表偏倚采用漏斗图进行定性评价。不同的电刺激(ES)参数(电流和电压)表现出抗菌活性,导致抑菌或杀菌效果。结论钛或钛基种植材料中的硒具有抗细菌生物膜的能力,其效果取决于施加的张力。ES和抗菌剂之间的相关性比单独使用ES更强。
{"title":"Efficacy of electrical stimulation for antimicrobial capacity of titanium materials implants: A systematic review and meta-analysis","authors":"Simone Kreve,&nbsp;Andréa C. dos Reis","doi":"10.1016/j.job.2025.100669","DOIUrl":"10.1016/j.job.2025.100669","url":null,"abstract":"<div><h3>Background</h3><div>Antimicrobial resistance undermines the effectiveness of drugs for treating implant-associated infections. Consequently, there is growing interest in identifying alternative methods to prevent and eliminate infections. The aim of this systematic review was to ascertain whether the electrical stimulation of titanium implants or titanium-based implant materials has antimicrobial properties against bacterial biofilms. The search was conducted in various databases, including PubMed/Medline, Web of Science, EMBASE, SCOPUS, and Google Scholar, in February 2024. In addition, a manual search of the reference lists of the included articles was conducted. The eligibility criteria included in vivo and in vitro studies evaluating the effects of electrical stimulation on titanium implants or titanium-based implant materials in reducing biofilm formation or adhesion as well as eradicating or reducing the viability of bacterial biofilms. The variability between studies was determined using the inverse variance method with random- and fixed-effects models. Heterogeneity was assessed using the I2 and prediction interval statistics. Publication bias was qualitatively evaluated using funnel plots.</div></div><div><h3>Highlights</h3><div>Different electrical stimulation (ES) parameters (current and voltage) exhibited antibacterial activity, resulting in either bacteriostatic or bactericidal effects.</div></div><div><h3>Conclusions</h3><div>ES in titanium or titanium-based implant materials confers antimicrobial capacity against bacterial biofilms, and its effectiveness depends on the applied tension. The association between ES and antimicrobials was more robust than with ES administered individually.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 2","pages":"Article 100669"},"PeriodicalIF":2.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898416","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}
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Journal of Oral Biosciences
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