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Mandibular morphogenesis: Genetic insights into malocclusion from EVC perspective 下颌形态发生:从EVC角度对错颌畸形的遗传见解
IF 2.3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-21 DOI: 10.1016/j.job.2025.100711
Nikta Gholampour , Amin Kalmari , Abasalt Hosseinzadeh Colagar , Valiollah Arash

Objectives

To investigate the association between an EVC gene single nucleotide polymorphism (rs1383180; G > A; R > Q) and mandibular skeletal malocclusion in the Mazandaran people of Northern Iran.

Methods

At the Arash Orthodontic Clinic in Babol, Iran, 393 individuals (148 controls, 119 with mandibular prognathism, and 126 with mandibular retrognathism) were screened for this case-control study. Cephalometric analysis, using Steiner parameters and “Wits” appraisal, verified skeletal relationships. Genomic DNA, extracted from gingival blood samples, was genotyped for rs1383180 using polymerase chain reaction-restriction fragment length polymorphism and validated using Sanger sequencing. Bioinformatics tools, including MUpro, iStable, DynaMut2, INPS-MD, SWISS-MODEL, ConSurf, PhD-SNPg, and Cscape, predicted the impact of the variant on protein function.

Results

The AA genotype of rs1383180 was significantly associated with mandibular prognathism (p = 0.036) and the mutant allele (A) trended towards significance (p = 0.081). There was no association with mandibular retrognathism. Bioinformatics analysis predicted that the G > A transition may disrupt the structure and stability of EVC protein. ConSurf indicated moderate evolutionary conservation and PhD-SNPg and Cscape identified rs1383180 as pathogenic and oncogenic.

Conclusion

The AA genotype of rs1383180 was associated with an increased risk of skeletal Class III malocclusion due to mandibular prognathism. As this genotype may disrupt Hedgehog signaling, this pathway may be influencing mandibular development.
目的探讨伊朗北部Mazandaran人EVC基因单核苷酸多态性(rs1383180; G >; A; R >; Q)与颌骨错颌畸形的关系。方法选取伊朗巴博勒Arash正畸诊所的393例患者进行病例对照研究,其中对照组148例,下颌前突119例,下颌后突126例。头部测量分析,使用斯坦纳参数和“Wits”评估,验证了骨骼关系。从牙龈血液样本中提取基因组DNA,使用聚合酶链反应-限制性片段长度多态性对rs1383180进行基因分型,并使用Sanger测序进行验证。生物信息学工具,包括MUpro、iStable、DynaMut2、INPS-MD、SWISS-MODEL、ConSurf、PhD-SNPg和Cscape,预测了变异对蛋白质功能的影响。结果rs1383180 AA基因型与下颌前突显著相关(p = 0.036),突变等位基因A有显著性趋势(p = 0.081)。与下颌颌后缩无关联。生物信息学分析预测,G >; A转变可能会破坏EVC蛋白的结构和稳定性。ConSurf显示了适度的进化保守性,PhD-SNPg和Cscape发现rs1383180具有致病性和致癌性。结论rs1383180 AA基因型与下颌前突所致骨骼III类错颌畸形的发病风险增高有关。由于该基因型可能破坏Hedgehog信号,因此该途径可能影响下颌发育。
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引用次数: 0
Propionic and acetic acids potentially compromise junctional epithelial barrier function and contribute to periodontitis progression 丙酸和乙酸可能损害结膜上皮屏障功能,促进牙周炎的进展
IF 2.3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-20 DOI: 10.1016/j.job.2025.100716
Takako Oikawa , Toshitaka Miura , Ting Wang , Takashi Yaegashi , Taichi Ishikawa , Daisuke Sasaki

Objectives

Periodontitis, a leading cause of tooth loss, is driven by pathogenic bacteria through classical virulence factors, including lipopolysaccharides, fimbriae, and proteases, and metabolic products such as short-chain fatty acids (SCFAs). Among these, butyric acid (BA) and lactic acid (LA) impair proliferation, migration, and inflammatory responses of gingival or junctional epithelial cells. However, the effects of other SCFAs, particularly propionic acid (PA) and acetic acid (AA), on the junctional epithelium remain unclear. In this study, the effects of PA and AA on murine JE-1 cells derived from the gingival junctional epithelium were examined.

Methods

JE-1 cells were treated with PA or AA. Wound healing, proliferation, viability, and cell cycle distribution were evaluated. The mRNA expression of adhesion molecules and cell cycle regulators was analyzed using quantitative reverse-transcription polymerase chain reaction.

Results

PA and AA markedly delayed wound closure and inhibited cell proliferation, without affecting cell viability. Both acids downregulated Integrin α6 and Integrin β4, induced G0/G1 arrest, decreased Ccnd1 expression, and increased p21 expression.

Conclusions

PA and AA impair wound repair, proliferation, and adhesion of junctional epithelial cells by altering the progression of the cell cycle and expression of adhesion-related genes. Together with prior findings on BA and LA, these results indicate that multiple SCFAs from periodontopathic bacteria contribute to weakening of the epithelial barrier, in vitro, highlighting the requirement for in vivo studies to confirm their roles in the pathogenesis of periodontitis.
目的牙周炎是牙齿脱落的主要原因,是由病原菌通过经典的毒力因子驱动的,包括脂多糖、菌毛、蛋白酶和代谢产物,如短链脂肪酸(SCFAs)。其中,丁酸(BA)和乳酸(LA)损害牙龈或结膜上皮细胞的增殖、迁移和炎症反应。然而,其他SCFAs,特别是丙酸(PA)和乙酸(AA)对结上皮的影响尚不清楚。本研究观察了PA和AA对小鼠龈结上皮JE-1细胞的影响。方法分别用PA或AA处理sje -1细胞。评估伤口愈合、增殖、活力和细胞周期分布。采用定量逆转录聚合酶链反应分析粘附分子和细胞周期调控因子的mRNA表达。结果spa和AA可明显延缓创面愈合,抑制细胞增殖,但不影响细胞活力。两种酸均下调整合素α6和整合素β4,诱导G0/G1阻滞,降低Ccnd1表达,增加p21表达。结论spa和AA通过改变细胞周期的进程和粘附相关基因的表达,影响创面修复、增殖和粘附能力。结合先前对BA和LA的研究结果,这些结果表明,来自牙周病细菌的多种SCFAs有助于在体外削弱上皮屏障,这突出了需要在体内研究来证实它们在牙周炎发病机制中的作用。
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引用次数: 0
Abaloparatide increases bone mass by increasing bone formation regardless of alendronate pretreatment in mice 无论阿仑膦酸钠预处理与否,阿巴巴拉肽通过增加骨形成来增加小鼠骨量
IF 2.3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-18 DOI: 10.1016/j.job.2025.100708
Akito Makino , Tomoka Hasegawa , Tomomaya Yamamoto , Hideko Takagi , Takeshi Iijima , Norio Amizuka
The effects of bisphosphonate pretreatment on the bone anabolic effects of abaloparatide (ABL) in mice were investigated. Mice were administered alendronate (ALN) at different doses for 21 days, followed by 28 days of ABL. ABL increased femoral bone mineral density at all ALN doses, with effects equal to or greater than those observed in mice without ALN. Histological analysis demonstrated that ABL increased ALPase- and PHOSPHO1-positive osteoblasts, irrespective of ALN pretreatment. However, the increase in TRAP-positive osteoclasts by ABL was attenuated at higher ALN doses. These findings suggest that ABL promotes bone formation in mice, independently of ALN pretreatment.
研究了双膦酸盐预处理对阿巴巴拉肽(ABL)骨合成代谢作用的影响。小鼠按不同剂量给予阿仑膦酸钠(ALN) 21天,随后给予ABL 28天。在所有ALN剂量下,ABL都增加了股骨骨矿物质密度,其效果等于或大于没有ALN的小鼠。组织学分析表明,与ALN预处理无关,ABL增加了ALPase-和phospho1阳性的成骨细胞。然而,ABL对trap阳性破骨细胞的增加在较高ALN剂量下减弱。这些发现表明,ABL促进小鼠骨形成,独立于ALN预处理。
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引用次数: 0
Intracellular mechanisms underlying modulation of inhibitory synaptic transmission by appetite-related peptides in the insular cortex 岛叶皮层食欲相关肽调控抑制性突触传递的细胞内机制
IF 2.3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-12 DOI: 10.1016/j.job.2025.100706
Yuka Nakaya , Masayuki Kobayashi

Background

The insular cortex (IC) integrates multimodal sensory inputs, including gustatory, visceral, nociceptive, and oral somatosensory information, and is widely regarded as the primary gustatory cortex. These functions are closely associated with feeding behaviors such as mastication, swallowing, and digestion, which are affected by appetite- and energy balance-related peptides.

Highlight

Orexin, leptin, and insulin have received particular attention because of their effects on IC circuits. Orexin, produced in the hypothalamus, activates postsynaptic phospholipase C, thereby inducing IP3 and elevating intracellular calcium levels. This effect facilitates inhibitory transmission to pyramidal neurons and promotes an excitatory drive onto interneurons. Leptin, secreted by adipocytes, facilitates inhibitory transmission from fast-spiking interneurons to pyramidal neurons via the presynaptic JAK2–PI3K–Akt signaling pathway. Similarly, insulin increases GABA release from fast spiking interneurons to pyramidal neurons in a PI3K–Akt-dependent manner. This collective peptidergic modulation leads to a net facilitation of inhibition within IC circuits, potentially reducing cortical excitability and output.

Conclusions

Given the involvement of the IC in the processing of sensory, interoceptive, and reward-related information, this peptidergic regulation likely influences a range of behaviors, including feeding, pain perception, and addiction. Elucidating these intricate mechanisms could facilitate the development of novel therapeutic interventions for disorders such as obesity, chronic pain, and substance dependence.
岛叶皮层(IC)整合了多模态的感觉输入,包括味觉、内脏、伤害和口腔体感信息,被广泛认为是初级味觉皮层。这些功能与咀嚼、吞咽和消化等摄食行为密切相关,这些行为受食欲和能量平衡相关肽的影响。由于维生素c、瘦素和胰岛素对IC电路的影响,它们受到了特别的关注。下丘脑产生的食欲素激活突触后磷脂酶C,从而诱导IP3并提高细胞内钙水平。这种作用促进了抑制性传递到锥体神经元,并促进了中间神经元的兴奋驱动。瘦素由脂肪细胞分泌,通过突触前JAK2-PI3K-Akt信号通路促进从快速尖峰的中间神经元到锥体神经元的抑制性传递。同样,胰岛素以pi3k - akt依赖的方式增加GABA从快速尖峰的中间神经元向锥体神经元的释放。这种集体的肽能调节导致IC电路内抑制的净促进,潜在地降低皮质兴奋性和输出。鉴于IC参与感觉、内感受和奖励相关信息的加工,这种肽能调节可能影响一系列行为,包括进食、疼痛感知和成瘾。阐明这些复杂的机制可以促进对肥胖、慢性疼痛和物质依赖等疾病的新型治疗干预措施的发展。
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引用次数: 0
Matrix metalloproteinase 9 expressed in satellite glial cells in the trigeminal ganglion contributes to tongue-cancer-associated pain 三叉神经节卫星胶质细胞中基质金属蛋白酶9的表达与舌癌相关疼痛有关
IF 2.3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-11 DOI: 10.1016/j.job.2025.100709
Ryosuke Takahashi , Suzuro Hitomi , Yoshinori Hayashi , Sho Sawada , Koichi Iwata , Masamichi Shinoda

Objectives

Matrix metalloproteinase 9 (MMP9) degrades extracellular matrix and it is involved in cancer angiogenesis, invasion, and metastasis. However, the function of MMP9 within the trigeminal ganglion (TG) in tongue-cancer-associated pain remains unclear. The objective of this study was to clarify the role of MMP9 in the TG in tongue-cancer-associated pain in rats.

Methods

Tongues were inoculated with squamous cell carcinoma (SCC) cells. Post–SCC inoculation, the tongues were subjected to mechanical stimulation using flat-tipped forceps and the mechanical head-withdrawal reflex threshold (MHWT) was measured. On Day 6, post-inoculation, the localization of MMP9 in the TG was identified, and its expression level was quantified. Additionally, MMP9 inhibitors were administered daily to the TG, post–SCC inoculation, and the MHWT was measured. Furthermore, MMP9 was administered daily to the TG of untreated rats, and the MHWT was measured.

Results

The MHWT decreased from Day 1, post–SCC inoculation. Activated satellite glial cells expressed MMP9, and the MMP9 level increased. Inhibition of MMP9 in the TG prevented the SCC-induced decrease in the MHWT from Day 6 onwards. Conversely, the administration of MMP9 to the TG led to a reduction in the MHWT in untreated rats.

Conclusion

MMP9, which originates from activated satellite glial cells in the TG, post–SCC inoculation, contributes to tongue-cancer-associated pain.
目的基质金属蛋白酶9 (MMP9)降解细胞外基质,参与肿瘤血管生成、侵袭和转移。然而,三叉神经节(TG)中MMP9在舌癌相关疼痛中的功能尚不清楚。本研究的目的是阐明MMP9在大鼠舌癌相关疼痛中TG中的作用。方法用鳞状细胞癌(SCC)细胞接种豚鼠。接种scc后,使用平尖钳对舌部进行机械刺激,并测量机械头退缩反射阈值(MHWT)。接种后第6天,鉴定MMP9在TG中的定位,并量化其表达水平。此外,每天给TG施用MMP9抑制剂,scc接种后,测量MHWT。此外,对未处理大鼠的TG每天给予MMP9,并测量MHWT。结果接种scc后,MHWT从第1天开始下降。激活的卫星胶质细胞表达MMP9,且MMP9水平升高。从第6天起,抑制TG中的MMP9可阻止scc诱导的MHWT下降。相反,在未治疗的大鼠中,给TG添加MMP9会导致MHWT的降低。结论mmp9起源于scc接种后TG中激活的卫星胶质细胞,参与了舌癌相关疼痛的发生。
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引用次数: 0
Development of micro-sequestra and associated histological changes in tooth extraction sockets of zoledronate-treated mice 唑来膦酸钠治疗小鼠拔牙窝微隔离的发生及相关组织学改变
IF 2.3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-11 DOI: 10.1016/j.job.2025.100710
Gaku Koizumi , Taku Murata , Akira Takigawa , Rina Yamada , Kasumi Shimizu , Usagi Hayashi , Akinobu Hayashi , Kazuto Kurohara , Naoya Arai

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.
目的给小鼠注射双膦酸盐并不一定会损害拔牙后的愈合。然而,目前尚不清楚双膦酸盐和盐水注射小鼠宏观愈合的拔牙窝之间是否存在组织学差异。方法单次静脉注射540 μg/kg唑来膦酸或生理盐水,1周后拔除上颌第一磨牙。通过显微计算机断层扫描和组织学检查拔牙槽的愈合情况。结果唑来膦酸和生理盐水对伤口愈合无明显影响。镜下观察,拔牙2周后拔牙窝软硬组织完全再生。然而,唑来膦酸处理小鼠口腔粘膜结缔组织中存在10 ~ 200 μm大小的小骨碎片。骨碎片有空的骨细胞腔隙,表明它们是微隔离的。多核巨细胞的聚集和假上皮瘤增生的接触与骨碎片有关。这些特征在拔牙后四周不存在。结论唑来膦酸治疗后,即使无骨坏死或骨暴露,拔牙槽内也存在微固支现象。尽管骨碎片和相关变化的意义尚不清楚,但这些发现可能有助于理解双磷酸盐引起的不良反应的亚临床状态。
{"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":"2025-11-11","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}
引用次数: 0
Proinflammatory effects of factor Xa on human dental pulp cells Xa因子对人牙髓细胞的促炎作用
IF 2.3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-04 DOI: 10.1016/j.job.2025.100707
Kento Nakanishi , Naoto Kamio , Takahiro Watanabe , Natsuko Furuya , Kosei Kuramochi , Joji Fukai , Makoto Suzuki , Arata Watanabe , Mizuki Matsui , Tatsu Okabe

Objectives

Dental pulp plays a crucial role in tooth homeostasis, and inflammation often leads to irreversible damage. Factor Xa (FXa), known for its role in coagulation, has recently been identified as an inflammatory mediator that acts via protease-activated receptor (PAR)-2 signaling. We herein investigated the PAR-2-mediated inflammatory response induced by FXa in human dental pulp cells (HDPC) by assessing COX-2 expression and prostaglandin E2 (PGE2) levels.

Methods

HDPCs were isolated from outgrowth cultures from extracted third molars and cultured in α-minimum essential medium containing 10 % fetal bovine serum. FXa was applied in a time- and concentration-dependent manner and COX-2 expression and PGE2 production were evaluated using real-time RT-PCR, western blotting, and enzyme immunoassays. PAR-2 localization in inflamed pulp tissue was assessed using immunohistochemistry. Intracellular kinase phosphorylation was analyzed using a phosphokinase array. Inhibitor experiments with AZ3451, rivaroxaban, and static were conducted to examine PAR-2, FXa, and signal transducers and activators of transcription (STAT)3 involvement in the signaling pathway.

Results

FXa promoted COX-2 expression and PGE2 production in HDPCs in a time- and concentration-dependent manner. Immunohistochemical analysis revealed localization of PAR-2-positive cells in inflamed human pulp tissues. Phosphokinase array analysis revealed enhanced STAT3 phosphorylation, and inhibition of PAR-2, FXa, and STAT3 suppressed COX-2 expression.

Conclusions

This study demonstrated that FXa induces COX-2 expression and PGE2 production in HDPCs via PAR-2 and STAT3 signaling. These findings enhance our understanding of pulp inflammation and may support the development of new therapeutic approaches for dental pulp preservation.
目的牙髓在维持牙齿体内平衡中起着至关重要的作用,而牙髓的炎症往往会导致不可逆的损伤。因子Xa (FXa)以其在凝血中的作用而闻名,最近被确定为一种炎症介质,通过蛋白酶激活受体(PAR)-2信号传导起作用。本文通过评估COX-2表达和前列腺素E2 (PGE2)水平,研究了FXa诱导的par -2介导的人牙髓细胞(HDPC)炎症反应。方法用含有10%胎牛血清的α-minimum essential培养基培养第三磨牙。FXa以时间和浓度依赖的方式应用,使用实时RT-PCR、western blotting和酶免疫分析评估COX-2的表达和PGE2的产生。使用免疫组织化学方法评估PAR-2在炎症牙髓组织中的定位。使用磷酸激酶阵列分析细胞内激酶磷酸化。用AZ3451、利伐沙班和static进行抑制剂实验,以检测PAR-2、FXa和信号转导器和转录激活器(STAT)3参与信号通路。结果fxa对HDPCs中COX-2的表达和PGE2的产生具有时间和浓度依赖性。免疫组织化学分析显示,炎症的人牙髓组织中存在par -2阳性细胞。磷酸激酶阵列分析显示STAT3磷酸化增强,抑制PAR-2、FXa和STAT3抑制COX-2表达。结论FXa通过PAR-2和STAT3信号通路诱导HDPCs中COX-2的表达和PGE2的产生。这些发现增强了我们对牙髓炎症的理解,并可能支持开发新的牙髓保存治疗方法。
{"title":"Proinflammatory effects of factor Xa on human dental pulp cells","authors":"Kento Nakanishi ,&nbsp;Naoto Kamio ,&nbsp;Takahiro Watanabe ,&nbsp;Natsuko Furuya ,&nbsp;Kosei Kuramochi ,&nbsp;Joji Fukai ,&nbsp;Makoto Suzuki ,&nbsp;Arata Watanabe ,&nbsp;Mizuki Matsui ,&nbsp;Tatsu Okabe","doi":"10.1016/j.job.2025.100707","DOIUrl":"10.1016/j.job.2025.100707","url":null,"abstract":"<div><h3>Objectives</h3><div>Dental pulp plays a crucial role in tooth homeostasis, and inflammation often leads to irreversible damage. Factor Xa (FXa), known for its role in coagulation, has recently been identified as an inflammatory mediator that acts via protease-activated receptor (PAR)-2 signaling. We herein investigated the PAR-2-mediated inflammatory response induced by FXa in human dental pulp cells (HDPC) by assessing COX-2 expression and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) levels.</div></div><div><h3>Methods</h3><div>HDPCs were isolated from outgrowth cultures from extracted third molars and cultured in α-minimum essential medium containing 10 % fetal bovine serum. FXa was applied in a time- and concentration-dependent manner and COX-2 expression and PGE<sub>2</sub> production were evaluated using real-time RT-PCR, western blotting, and enzyme immunoassays. PAR-2 localization in inflamed pulp tissue was assessed using immunohistochemistry. Intracellular kinase phosphorylation was analyzed using a phosphokinase array. Inhibitor experiments with AZ3451, rivaroxaban, and static were conducted to examine PAR-2, FXa, and signal transducers and activators of transcription (STAT)3 involvement in the signaling pathway.</div></div><div><h3>Results</h3><div>FXa promoted COX-2 expression and PGE<sub>2</sub> production in HDPCs in a time- and concentration-dependent manner. Immunohistochemical analysis revealed localization of PAR-2-positive cells in inflamed human pulp tissues. Phosphokinase array analysis revealed enhanced STAT3 phosphorylation, and inhibition of PAR-2, FXa, and STAT3 suppressed COX-2 expression.</div></div><div><h3>Conclusions</h3><div>This study demonstrated that FXa induces COX-2 expression and PGE<sub>2</sub> production in HDPCs via PAR-2 and STAT3 signaling. These findings enhance our understanding of pulp inflammation and may support the development of new therapeutic approaches for dental pulp preservation.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 4","pages":"Article 100707"},"PeriodicalIF":2.3,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145474052","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
Piezo1 negatively regulates proliferation, but enhances mineralization in human cementoblasts Piezo1负性调节增殖,但增强人成水泥细胞的矿化
IF 2.3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-01 DOI: 10.1016/j.job.2025.100705
Toshihiro Hasegawa , Takehito Ouchi , Ryuya Kurashima , Maki Kimura , Seiji Asoda , Taneaki Nakagawa , Yoshiyuki Shibukawa

Objectives

Cementoblasts play essential roles in secreting collagenous and non-collagenous matrix proteins and in mineralization to produce cementum. Cementum is a mineralized tissue deposited in layers on the surface of the tooth root, where it is subjected throughout life to mechanical stresses including chewing and occlusal forces. To date, the detailed mechanosensitivity mechanisms regulating cementoblasts remain unclear.

Methods

We investigated cellular functions driven by mechanosensitive processes in human cementoblasts (HCEM) by analyzing protein expression using immunofluorescence staining and mechanical stimulation-induced Ca2+ signaling by measuring intracellular free Ca2+ concentration ([Ca2+]i) using the Ca2+ indicator fura-2. We also assessed cell proliferation modulation using colony-forming unit fibroblast (CFU–F) analysis, and mineralization efficacy using Alizarin Red and von Kossa staining.

Results

HCEM were immunopositive for cementoblast marker proteins, cementum attachment protein, and cementum protein 1, and the mechanosensitive cation channels Piezo1 and Piezo2. Both direct mechanical stimulation and pharmacological stimulation with the Piezo1 activator Yoda1 elicited transient increases in [Ca2+]i, which were significantly suppressed by Dooku1, a pharmacological Yoda1 inhibitor. In the CFU-F assay, colony formation was significantly enhanced by treatment with pharmacological Piezo1 inhibitors, and by GsMTx4, Dooku1, and Piezo1 gene silencing, but was suppressed by Yoda1. HCEM mineralization efficacy was significantly promoted by Yoda1 but significantly suppressed by GsMTx4, Dooku1, and Piezo1 gene silencing.

Conclusions

Piezo1 suppresses colony formation, but activates HCEM-mediated mineralization, suggesting that Piezo1-induced Ca2+ signaling plays an important role in cementum mineralization and deposition by cementoblasts.
目的成骨水泥细胞在分泌胶原和非胶原基质蛋白及矿化生成骨水泥中发挥重要作用。牙骨质是一种矿化组织,分层沉积在牙根表面,在那里它终生受到包括咀嚼和咬合力在内的机械应力。迄今为止,调节成水泥细胞的详细机械敏感性机制尚不清楚。方法通过免疫荧光染色分析人成水泥细胞(HCEM)的蛋白表达,利用Ca2+指示剂fura-2测量细胞内游离Ca2+浓度([Ca2+]i),通过机械刺激诱导的Ca2+信号传导,研究机械敏感过程驱动的细胞功能。我们还使用集落形成单位成纤维细胞(CFU-F)分析评估了细胞增殖调节,并使用茜素红和von Kossa染色评估了矿化效果。结果小鼠成骨水泥标记蛋白、骨水泥附着蛋白、骨水泥蛋白1及机械敏感阳离子通道Piezo1和Piezo2均呈免疫阳性。Piezo1激活剂Yoda1的直接机械刺激和药理学刺激都能引起[Ca2+]i的短暂增加,而这种增加被Yoda1药理学抑制剂Dooku1显著抑制。在CFU-F实验中,使用药理Piezo1抑制剂以及GsMTx4、Dooku1和Piezo1基因沉默治疗可显著增强菌落形成,但被Yoda1抑制。Yoda1显著促进HCEM矿化效果,而GsMTx4、Dooku1和Piezo1基因沉默显著抑制HCEM矿化效果。结论piezo1抑制骨水泥集落形成,但激活hcem介导的矿化,提示piezo1诱导的Ca2+信号在成骨水泥矿化和沉积中起重要作用。
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引用次数: 0
Dextrin utilization in Streptococcus pyogenes pathogenesis and growth 糊精在化脓性链球菌发病和生长中的利用
IF 2.3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-10-22 DOI: 10.1016/j.job.2025.100704
Yujiro Hirose , Victor Nizet , Shigetada Kawabata

Background

Streptococcus pyogenes has several clinical manifestations, from mild pharyngitis to life-threatening necrotizing fasciitis. Nutrient conditions strongly influence its virulence, and the ability to metabolize dextrin contributes to growth and pathogenicity. Since dextrin-dependent phenotypes link metabolic adaptation with virulence regulation, reviewing the current knowledge is essential for understanding how carbohydrate utilization shapes S. pyogenes pathogenesis and proliferation.

Highlight

Animal models have demonstrated that the maltose/dextrin utilization operon enhances fitness and is co-activated with major toxins at infection sites. System-level analyses have shown that dextrin induces the nga–ifsslo operon and activates CovRS-associated modules, a regulatory system central to virulence control. Dextrin also promotes in vitro growth, with genome-scale metabolic modeling implicating increased arginine metabolism in this phenotype. Collectively, these results suggest that dextrin acts as a regulatory cue to reprogram virulence and metabolic capacity.

Conclusion

Dextrin utilization shapes both the growth and virulence of S. pyogenes. Although the mechanisms remain incompletely defined, integrating metabolic modeling with experimental approaches will be crucial for clarifying how carbohydrate use drives invasive diseases.
背景化脓性链球菌有几种临床表现,从轻微的咽炎到危及生命的坏死性筋膜炎。营养条件强烈影响其毒力,代谢糊精的能力有助于生长和致病性。由于糊精依赖表型将代谢适应与毒力调节联系起来,因此回顾当前的知识对于理解碳水化合物利用如何影响化脓链球菌的发病机制和增殖是必不可少的。动物模型表明,麦芽糖/糊精利用操纵子增强了适应度,并与感染部位的主要毒素共同激活。系统级分析表明,糊精诱导nga - ifs - slow操纵子并激活covrs相关模块,这是毒力控制的核心调控系统。糊精也促进体外生长,基因组尺度的代谢模型表明这种表型中精氨酸代谢增加。总之,这些结果表明,糊精作为一个调控线索,重新编程毒力和代谢能力。结论糊精的利用影响化脓性葡萄球菌的生长和毒力。尽管机制尚未完全确定,但将代谢模型与实验方法相结合对于阐明碳水化合物使用如何驱动侵袭性疾病至关重要。
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引用次数: 0
Hydroxyapatite-based cavitary varnish derived from eggshells: An in vitro analysis of dentin surface 从蛋壳中提取的羟基磷灰石基口腔清漆:牙本质表面的体外分析
IF 2.3 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-10-17 DOI: 10.1016/j.job.2025.100703
Ana Cláudia Dalmolin , Márcia Thaís Pochapski , Geovana Stafin , Carlos Guilherme Murr , Sandra Regina Masetto Antunes , Fábio André dos Santos

Objectives

We aimed to evaluate the effectiveness of a cavitary varnish containing an experimental eggshell-derived hydroxyapatite (HA) on dentin surfaces.

Methods

One hundred and twenty bovine dentin samples were prepared and randomly assigned to five groups: distilled water (DW); cavitary varnish (CV); Colgate® Sensitive Pro-Relief™ (CS); commercial HA NanoP™ (NP); and cavitary varnish with experimental HA. After treatment, samples were subjected to simulated brushing. Surface roughness, morphology, chemical composition, dentin tubule diameter, and permeability were evaluated. Data were analyzed using two-way analysis of variance with Bonferroni post-hoc test.

Results

HA samples without brushing exhibited the highest surface roughness. Scanning electron microscopy revealed complete dentinal tubule occlusion in HA samples, which persisted after brushing, whereas other groups showed partial occlusion or exposed tubules. Chemical analysis demonstrated lower phosphorus levels in HA samples without brushing, with an increase after brushing; NP and HA exhibited the highest phosphorus levels after brushing. DW samples showed the highest intertubular calcium levels, whereas CS samples showed the lowest levels after brushing. DW presented the largest tubule diameters without brushing, while brushing significantly increased the tubule diameters in all groups except DW group. Regarding dentin permeability, HA samples had significantly reduced hydraulic conductance compared with DW samples without brushing, with a performance comparable to commercial products; after brushing, no significant differences were detected among groups.

Conclusions

Eggshell-derived HA promoted complete and persistent dentinal tubule occlusion and significantly reduced the permeability, even after brushing, confirming its potential as a sustainable and cost-effective biomaterial for dental applications.
目的评价含实验性蛋壳衍生羟基磷灰石(HA)的牙本质表面牙本质清漆的效果。方法制备牛牙本质样品120份,随机分为5组:蒸馏水组(DW);空腔清漆(CV);高露洁®Sensitive Pro-Relief™;商用HA NanoP™(NP);和实验HA的空腔清漆。处理后,对样品进行模拟刷牙。评估了表面粗糙度、形貌、化学成分、牙本质小管直径和渗透率。数据分析采用Bonferroni事后检验的双向方差分析。结果未涂刷的样品表面粗糙度最高。扫描电镜显示,HA组牙本质小管完全闭塞,刷牙后仍存在,而其他组牙本质小管部分闭塞或暴露。化学分析表明,未涂刷的HA样品中磷含量较低,涂刷后磷含量增加;刷刷后,NP和HA的磷含量最高。DW样品的管间钙含量最高,而CS样品的管间钙含量在刷牙后最低。未涂刷DW组的小管直径最大,除DW组外,涂刷均显著增加各组小管直径。在牙本质渗透性方面,与未涂刷的DW样品相比,HA样品的水力导度显著降低,其性能与商业产品相当;刷牙后,各组间无显著差异。结论seggshell源性透明质酸可促进牙本质小管的完全和持久咬合,即使在刷牙后也能显著降低其渗透性,证实了其作为一种可持续的、具有成本效益的牙科生物材料的潜力。
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Journal of Oral Biosciences
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