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Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss

International Journal of Oral Science 2015年第4期7卷 242-249页

作者： Ujjal K Bhawal Hye-Jin Lee Kazumune Arikawa Michiharu Shimosaka Masatoshi Suzuki Toshizo Toyama Takenori Sato Ryota Kawamata Chieko Taguchi Nobushiro Hamada Ikuo Nasu Hirohisa Arakawa Koh Shibutani Department of Biochemistry and Molecular Biology Nihon University School of Dentistry at Matsudo Research Institute of Oral Health Nihon University School of Dentistry at Matsudo Department of Oral Health Graduate School of DentistryKanagawa Dental University Department of Dental Hygiene Howon University Department of Preventive and Public Oral Health Nihon University School of Dentistry at Matsudo Department of Anesthesiology Nihon University School of Dentistry at Matsudo Department of Infection Control Division of MicrobiologyKanagawa Dental University Department of Radiopraxis Science Kanagawa Dental University

Osteoclasts are bone-specific multinucleated cells generated by the differentiation of monocyte/macrophage lineage precursors. Regulation of osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone-lytic diseases. Periodontitis is an inflammatory disease characterized by extensive bone resorption. In this study, we investigated the effects of sodium fluoride （NaF） on osteoclastogenesis induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. NaF strongly inhibited the P. gingivalis-induced alveolar bone loss. That effect was accompanied by decreased levels of cathepsin K, interleukin （IL）-1β, matrix metalloproteinase 9 （MMP9）, and tartrate-resistant acid phosphatase, which were up-regulated during P. gingivalis-induced osteoclastogenesis. Consistent with the in vivo anti-osteoclastogenic effect, NaF inhibited osteoclast formation caused by the differentiation factor RANKL （receptor activator of nuclear factor KB ligand） and macrophage colony-stimulating factor （M-CSF）. The RANKL-stimulated induction of the transcription factor nuclear factor of activated T cells （NFAT） cl was also abrogated by NaF. Taken together, our data demonstrate that NaF inhibits RANKL-induced osteoclastogenesis by reducing the induction of NFATcl, ultimately leading to the suppressed expression of cathepsin K and MMP9. The in vivo effect of NaF on the inhibition of P. gingivalis-induced osteoclastogenesis strengthens the potential usefulness of NaF for treating periodontal diseases.

关键词： alveolar bone loss osteoclasts Porphyromonas gingivalis sodium fluoride

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Intragingival injection of Porphyromonas gingivalis-derived lipopolysaccharide induces a transient increase in gingival tumour necrosis factor-a, but not interleukin-6,in anaesthetised rats

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International Journal of Oral Science 2015年第3期7卷 155-160页

作者： Hiroko Taguchi Yuri Aono Takayuki Kawato Masatake Asano Noriyoshi Shimizu Tadashi Saigusa Department of Orthodontics Nihon University School of Dentistry Department of Pharmacology Nihon University School of Dentistry at Matsudo Department of Pharmacology Nihon University School of Dentistry Department of Oral Health Sciences Nihon University School of Dentistry Department of Pathology Nihon University School of Dentistry

This study used in vivo microdialysis to examine the effects of intragingival application of lipopolysaccharide（LPS） derived from Porphyromonas gingivalis（Pg-LPS） on gingival tumour necrosis factor（TNF）-a and interleukin（IL）-6 levels in rats. A microdialysis probe with an injection needle attached to the surface of the dialysis membrane was implanted into the gingiva of the upper incisor. For comparison, the effects of LPS derived from Escherichia coli（Ec-LPS） on IL-6 and TNF-a levels were also analysed. Pg-LPS（1 mg/1 m L） or Ec-LPS（1 or 6 mg/1 m L） was applied by microsyringe, with gingival dialysates collected every hour. Enzyme-linked immunosorbent assay（ELISA） revealed that gingival dialysates contained approximately 389 pg？m L21 of IL-6 basally; basal TNF-a levels were lower than the detection limit of the ELISA. Pg-LPS failed to alter IL-6 levels but markedly increased TNF-a levels, which remained elevated for 2 h after treatment. Neither IL-6 nor TNF-a were affected by Ec-LPS. Reverse transcriptase-polymerase chain reaction（RT-PCR） analysis revealed that the gingiva expresses Toll-like receptor（TLR） 2 and TLR4 m RNA. Immunohistochemical examination showed that TLR2 and TLR4 are expressed by gingival epithelial cells. The present study provides in vivo evidence that locally applied Pg-LPS, but not Ec-LPS, into the gingiva transiently increases gingival TNF-a without affecting IL-6. The present results suggest that TLR2 but not TLR4 expressed on gingival epithelial cells may mediate the Pg-LPS-induced increase in gingival TNF-a in rats.

关键词： Porphyromonas gingivalis lipopolysaccharide gingiva tumour necrosis factor-a microdialysis

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Update on the pathological roles of prostaglandin E_(2) in neurodegeneration in amyotrophic lateral sclerosis

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Translational Neurodegeneration 2023年第1期12卷 464-478页

作者： Hiroshi Nango Komugi Tsuruta Hiroko Miyagishi Yuri Aono Tadashi Saigusa Yasuhiro Kosuge Laboratory of Pharmacology School of PharmacyNihon University7-7-1 NarashinodaiFunabashi-ShiChiba 274-8555Japan Department of Pharmacology School of Dentistry at MatsudoNihon University2-870-1 SakaechonishiMatsudo-ShiChiba 271-8587Japan

Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease characterized by selective degeneration of upper and lower motor *** pathogenesis of ALS remains largely unknown;however,inflammation of the spinal cord is a focus of ALS research and an important pathogenic process in *** E_(2)(PGE_(2))is a major lipid mediator generated by the arachidonic-acid cascade and is abundant at inflammatory ***_(2)levels are increased in the postmortem spinal cords of ALS patients and in ALS model *** therapeutic effects have been obtained in ALS model mice using cyclooxygenase-2 inhibitors to inhibit the biosynthesis of PGE_(2),but the usefulness of this inhibitor has not yet been proven in clinical *** this review,we present current evidence on the involvement of PGE_(2)in the progression of ALS and discuss the potential of microsomal prostaglandin E syn-thase(mPGES)and the prostaglandin receptor E-prostanoid(EP)2 as therapeutic targets for *** pathways involving prostaglandin receptors mediate toxic effects in the central nervous *** some situations,however,the receptors mediate neuroprotective *** recent studies demonstrated that levels of mPGES-1,which catalyzes the final step of PGE_(2)biosynthesis,are increased at the early-symptomatic stage in the spinal cords of transgenic ALS model mice carrying the G93A variant of superoxide *** addition,in an experimental motor-neuron model used in studies of ALS,PGE_(2)induces the production of reactive oxygen species and subsequent caspase-3-de-pendent cytotoxicity through activation of the EP2 ***,this PGE_(2)-induced EP2 up-regulation in motor neurons plays a role in the death of motor neurons in ALS model *** understanding of the pathophysiologi-cal role of PGE_(2)in neurodegeneration may provide new insights to guide the development of novel therapies for ALS.

关键词： Prostaglandin E_(2) Amyotrophic lateral sclerosis Motor neuron death E-prostanoid receptor Microsomal prostaglandin E synthetase-1

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Lipopolysaccharide Enhances the Production of Nicotine-Induced Prostaglandin E2 by an Increase in Cyclooxygenase-2 Expression in Osteoblasts

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Acta Biochimica et Biophysica Sinica 2007年第3期39卷 163-172页

作者： Maiko SHOJI Natsuko TANABE Narihiro MITSUI Naoto SUZUKI Osamu TAKEICHI Tomoko KATONO Akira MOROZUMI Masao MAENO Department of Oral Health Sciences Nihon University School of DentistryTokyo 101-8310Japan Division of Functional Morphology Dental Research Center.Nihon University School ofDentistryTokyo 101-8310Japan nihon university Grndudte school of dentistry Tokyo 101-8310Japan Division of Functional Morphology Dental Research Center.Nihon University School of DentistryTokyo 101-8310Japan Department of Endodontics Nihon University School of DentisityTokyo 101-8310Japan Division of Advanced Dental Treatment Dental Research CenterNihon University School of DentistryTokyo 101-8310Japan nihon university graduate school of dentistry Tokyo 101-8310Japan

Previous studies have indicated that lipopolysaccharide（LPS）from Gram-negative bacteria inplaque induces the release of prostaglandin E2（PGE2）,which promotes alveolar bone resorption in periodontitis,and that tobacco smoking might be an important risk factor for the development and severity of *** determined the effect of nicotine and LPS on alkaline phosphatase（ALPase）activity,PGE2production,and the expression of cyclooxygenase（COX-1,COX-2）,PGE2receptors Ep1-4,and macrophage colonystimulating factor（M-CSF）in human osteoblastic Saos-2 *** cells were cultured with 10-3M nicotinein the presence of 0,1,or 10μg/ml LPS,or with LPS *** activity decreased in cells cultured withnicotine or LPS alone,and decreased further in those cultured with both nicotine and LPS,whereas PGE2production significantly increased in the former and increased further in the *** itself,nicotine did notaffect expression of COX-1,COX-2,any of the PGE2receptors,or M-CSF,but when both nicotine and LPSwere present,expression of COX-2,Ep3,Ep4,and M-CSF increased *** addition of10-4M indomethacin eliminated the effects of nicotine and LPS on ALPase activity,PGE2production,and M-CSF *** of protein kinase A was high in cells cultured with nicotine and *** suggest that LPS enhances the production of nicotine-induced PGE2by an increase in COX-2 expres-sion in osteoblasts,that nicotine-LPS-induced PGE2interacts with the osteoblast Ep4 receptor primarily inautocrine or paracrine mode,and that the nicotine-LPS-induced PGE2then decreases ALPase activity andincreases M-CSF expression.

关键词： nicotine lipopolysaccharide prostaglandin E2 cyclooxygenase-2 Ep4 receptor

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The Effectiveness of a Portable Fluorescence Spectrophotometer for Early Detection of Oral Cancer

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Open Journal of Stomatology 2022年第1期12卷 30-31页

作者： Katsuhiro Asaka Akira Fukatsu Chiaki Komine Laboratory Medicine for dentistry Graduate School of Dentistry at Matsudo Nihon University School of Dentistry at Matsudo Matsudo Japan Department of Laboratory Medicine and dentistry for the Compromised Patient Nihon University School of Dentistry at Matsudo Matsudo Japan

Purpose: To investigate whether photodynamic diagnosis (PDD) using a portable fluorescence spectrophotometer (FC-1) can easily and objectively discriminate between normal and tumor cells at the dental chairside, and to further compare it with PDD that requires speculum examination by focusing on protoporphyrin IX (PPIX). Methods: Three cell lines (2 human oral squamous cell carcinoma-derived cell lines, HSC-2 and HSC-3 cells, and oral keratinocytes, HOK cells) were cultured. 5-Aminolevulinic acid hydrochloride (5-ALA) and deferoxamine mesylate (DFO) were mixed in DMEM, and the mixture was set to Control (DMEM only) and PDD (5-ALA+DFO) groups. And then, a fluorescence was measured under room temperature (RT) and 37°C (Incubation) by using FC-1. In this study, the two conditions were combined with the Control and PDD groups to form the Control/RT, Control/Incubate, PDD/RT, and PDD/Incubate groups. Additionally, the amount of singlet oxygen (1O2) generated by irradiation with 405 nm LED was measured using electron spin resonance spectroscopy to detect PPIX in the cell supernatant after 24 hours. Results: In HSC-2 and HSC-3, the fluorescence intensity values increased significantly at 2 hours between the Control/RT and PDD/RT groups. In addition, there was a significant difference between HSC-2 and HSC-3 compared to HOK. In all cell lines, the fluorescence intensity values of the PDD/Incubate group were significantly higher than those of the PDD/Control group. The amount of 1O2 generated by 405 nm LED irradiation was higher in the cell supernatants of all cell lines in the order of Control/RT Conclusion: It is suggested that PDD using FC-1 can clearly distinguish between normal cells and tumor cells in vitro studies using cell lines at 2 hours und

关键词： Photodynamic Diagnosis Portable Fluorescence Spectrophotometer Oral Cancer Protoporphyrin IX

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Influence of Masticatory Functional Loss on the Remodeling of Alveolar Bone in Rats

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Open Journal of Stomatology 2020年第12期10卷 341-359页

作者： Kei Ogawa Takamichi Yamada Norimitsu Hirai Wataru Morita Yurie Okada Seiko Yamamoto-Nemoto Takehiko Shimizu Department of Pediatric dentistry Nihon University School of Dentistry at Matsudo Matsudo Chiba Japan nihon university Research Institute of Oral Science Matsudo Chiba Japan Department of Pediatric dentistry Nihon University Graduate School of Dentistry at Matsudo Matsudo Chiba Japan

There is plenty of literature on masticatory function and its impact on maxillofacial development. However, the influence of masticatory hypofunction on bone turnover in the alveolar bone has hardly been studied. This study aimed to clarify the influence of tooth loss and soft diet on the alveolar bone turnover during the growth period. Three-week-old Wistar rats were randomly divided into the following three groups: Hard diet group (rats raised on solid standard diet), Powder diet group (rats raised on powdered standard feed diet), and Extraction group (rats raised on powdered standard diet with maxillary molars extraction). BV, BMC, and BMD in the cancellous bone of M1 were measured using micro-CT analysis. To analyze the histological bone turnover, we prepared non-decalcified thin sections of alveolar cancellous bone when rats were 20 weeks old. On three-dimensional constructed images, the experimental groups (the Powder diet and Extraction groups) showed expansion of the medullary cavity of the interradicular septum of the first molar compared to controls (the Hard diet group). BV, BMC, and BMD were significantly lower in the experimental groups, with the difference from controls being greater in the Extraction group. On histomorphometric analysis, the bone mass parameters, bone formation parameters, and bone mineralization parameters were significantly lower in the experimental groups compared to controls. The bone resorption parameters were significantly higher in the experimental groups. From this study, we found that soft diet and tooth loss might worsen the bone microstructure, reduce osteogenesis, and promote bone resorption in alveolar bone.

关键词： Rats Alveolar Bone Powder Diet Extraction of Molars Bone Histomorphometry

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Minor Salivary Gland Tumors: A Retrospective Study of 37 Cases

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Open Journal of Stomatology 2022年第12期12卷 363-371页

作者： Hiroshi Yamamoto Yukiko Iizuka Erika Iwai Shu Fushimi Ryutaro Tsuchimoto Minami Akagi Shina Kato Kunio Hayashi Mitsuko Nakayama Masaaki Suemitsu Tadahiko Utsunomiya Yoshikazu Nakayama Kayo Kuyama Masamichi Komiya Department of Oral Surgery Nihon University School of Dentistry at Matsudo Chiba Japan nihon university graduate school of dentistry at matsudo Oral and Maxillofacial Surgery Chiba Japan Department of Pathology Nihon University School of Dentistry at Matsudo Chiba Japan nihon university graduate school of dentistry at matsudo Oral Pathology Chiba Japan

Salivary gland tumors represent 2% - 6.5% of all head and neck tumors. Since salivary gland tumors have various clinical features and histological types, it is often difficult to diagnose and treat them. The aim of this study was to conduct a retrospective clinical-statistical analysis of 37 minor salivary gland tumors (MSGTs) treated in the Department of Oral Surgery at nihon university school of dentistry at matsudo over a 16-year period. The frequencies and distributions of sex, age, occurrence site, preoperative examination (fine needle cytology and/or biopsy), treatment, and prognosis of the tumors were analyzed and compared with previous reports. The average age at diagnosis was 58.1 years (range 22 - 91 years). The peak occurrence of tumors was in the sixties (10 cases, 27.0%), followed by the forties (8 cases, 21.6%) and the seventies (7 cases, 18.9%). The average age of patients with benign tumors was 56.8 years (range 22 - 91 years). For malignant tumors, the average age was 61.7 years (range 42 - 81 years). The male-female ratio was 1:2.1 for all minor salivary gland tumors, 1:2.4 for benign tumors, and 1.5:1 for malignant tumors. There were 27 (73.0%) benign and 10 (27.0%) malignant tumors. Pleomorphic adenoma (PA) was the most common tumor (24 (64.9%) cases). Most salivary gland tumors originated from the palate (21 cases, 56.8%);the second most common site was the buccal mucosa (14 cases, 37.8%). For most patients, an intraoral mass was the primary presentation, and the second most common symptom was swelling. Surgical treatment was performed for all cases, both benign and malignant tumors. There was one case of local recurrence of PA, as well as one of multiple lung metastases after surgery for adenoid cystic carcinoma. Diagnosis and treatment of MSGTs are often delayed because the patients have few symptoms, and it is difficult to distinguish benign from malignant tumors. More cases need to be examined in the future, and the diagnostic accuracy of im

关键词： Minor Salivary Gland Tumor Clinical Statistics Intraoral Japanese

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Development of a Photodynamic Diagnosis Method for Oral Squamous Cell Carcinoma Using 5-Aminolevulinic Acid and a Luminescence Plate Reader

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Open Journal of Stomatology 2021年第9期11卷 325-340页

作者： Hiroko Omori Chiaki Komine Laboratory Medicine for dentistry Graduate School of Dentistry at Matsudo Nihon University Matsudo Japan Department of Laboratory Medicine and dentistry for the Compromised Patient Nihon University Matsudo Japan

Purpose: To establish a simple and accurate photodynamic diagnosis (PDD) method for oral squamous cell carcinoma (OSCC). Methods: OSCC cell lines HSC-2, HSC-3, HSC-4, and Sa3, and normal human oral keratinocytes (HOK) were used. First, we examined the amount of cells needed to detect differences in fluorescence intensities for PDD. OSCC cell lines were adjusted to concentrations of 1 × 104 (104), 1 × 105 (105), and 1 × 106 (106) cells/ml. The experimental groups comprised a group with 5-aminolevulinic acid (5-ALA (+)), and a group without 5-ALA (5-ALA (-)). For each OSCC cell line, 100 μl of each concentration of cells of the 5-ALA groups was seeded onto fluorescence plates, and fluorescence intensity was measured at 60-min intervals for 240 min. Results are expressed as the ratio of fluorescence intensity in 5-ALA (+) to 5-ALA (-). As cells at the concentration of 106 cells/ml provided the clearest results, fluorescence intensities of all cell lines were measured using this concentration at 20-min intervals for 700 min using the same methods. Results: The 5-ALA (+) to (-) ratio increased in a cell concentration-dependent manner at 240 min;the ratio was highest with 106 cells/ml and lowest with 104 cells/ml. With 106 cells/ml in the 5-ALA (+) group, fluorescence intensity increased in a metabolic time-dependent manner;the increase was highest in HSC-2 cells, followed by HSC-4 cells, HSC-3 cells, Sa3 cells, and HOK. Fluorescence intensity was significantly enhanced after 40 min in HSC-2, HSC-3, and HSC-4 cells, after 60 min in Sa3 cells, and after 100 min in HOK compared to the 5-ALA (-) group (P Conclusion: Early detection of OSCC is possible by screening only micro

关键词： Luminescence Plate Reader 5-Aminolevulinic Acid (5-ALA) Photodynamic Diagnosis (PDD) Oral Squamous Cell Carcinoma (OSCC)

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Comparative Cytological and Histopathological Study of Peri-Implantitis and Periodontitis

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Open Journal of Stomatology 2023年第11期13卷 385-395页

作者： Masaaki Suemitsu Yoshikazu Nakayama Mao Yamamoto Mitsuko Nakayama Tadahiko Utsunomiya Kayo Kuyama Department of Pathology School of Dentistry at Matsudo Nihon University Chiba Japan Department of Oral Pathology Nihon University Graduate School Dentistry at Matsudo Chiba Japan

Peri-implant diseases, such as peri-implant mucositis and peri-implantitis, pose significant challenges to the long-term prognosis of dental implants. This study aimed to comprehensively compare peri-implantitis with periodontitis from cytological and histopathological perspectives, shedding light on the morphological characteristics associated with peri-implantitis. Thirteen patients, including six with peri-implantitis and seven with periodontitis, were included in the study. Cytological examination of affected gingival mucosa revealed distinct differences between the two conditions. Peri-implantitis exhibited an inflammatory background predominantly composed of neutrophils with lobulated nuclei, accompanied by stratified squamous epithelial cells showing signs of keratinization. In contrast, periodontitis showed a similar neutrophilic inflammatory background but with non-keratinized epithelial cells. Histopathological examination further confirmed these differences, with peri-implantitis showing keratinized epithelium in the inner epithelial layer. This histological finding aligns with the notion that peri-implantitis has a distinct mucosal profile compared to periodontitis. Additionally, cytological analysis revealed that peri-implantitis had a lower occurrence rate of Light green-positive cells, indicating a tendency toward keratinization. This finding suggests that the presence of keratinized mucosa might be associated with peri-implant health, although further research is needed to clarify this relationship. Overall, this study demonstrates the potential of cytological examination and Papanicolaou staining for assessing mucosal inflammatory conditions and distinguishing between keratinized and non-keratinized cells. These findings underscore the utility of oral mucosal smears as a valuable tool for diagnosing peri-implantitis and enhancing our understanding of its pathogenesis.

关键词： Peri-Implant Disease Peri-Implantitis Oral Cytology

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Palisaded encapsulated neuroma of the upper lip

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Open Journal of Stomatology 2012年第3期2卷 228-233页

作者： Kayo Kuyama Hirotaka Oomine Yan Sun Masanobu Wakami Hirotsugu Yamamoto Department of Crown and Bridge Prosthodontics Nihon University School of Dentistry at Matsudo Matsudo Japan Department of Diagnostic Pathology Hospital of Nihon University School of Dentistry at Matsudo Matsudo Japan Department of Maxillo-Facial Orthodontics Nihon University School of Dentistry at Matsudo Department of Oral Pathology Nihon University School of Dentistry at Matsudo Matsudo Japan

Palisaded encapsulated neuroma (PEN;solitary circumscribed neuroma) is a benign and hyperplastic lesion consisting of Schwann cells. PEN of the lower lip was reported by Tomich and Moll [1] 35 years ago. However, the accumulation of the information about PEN which occurred in the oral mucosa was not enough. This article describes a case of a PEN on the upper lip of a 41-year-old woman. The lesion with 0.7 cm diameter was performed excisional biopsy. Histologically, the tumor was almost circumscribed by thin fibrous capsule, and consisted of diffusely and dense proliferation of the spindle shape cells arranged in interlacing fascicles. Focal suggestions of nuclear pal-isaded growth were indicated within the tumor. Immunohistochemicallly, the fascicles of tumor cells were positive for S-100 protein, and vimentin and negative for α-actin and GFAP. A few numbers of axons were demonstrated by anti-neurofilament antibody in this lesion. Therefore, the definitive diagnosis was PEN.

关键词： Palisaded Encapsulated Neuroma Solitary Circumscribed Neuroma Immunohistochemistry

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