論文 - 山本　直史

Establishment of a rapid and quantitative method for detecting the range of infection exposure in preclinical dental education. 国際誌

Ayaka Ueda, Yuki Shinoda-Ito, Kazu Takeuchi-Hatanaka, Takashi Ito, Shintaro Ono, Kimito Hirai, Kazuhiro Omori, Tadashi Yamamoto, Shogo Takashiba

BMC oral health   25 ( 1 )   199 - 199   2025年2月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUNDS: Safe dental treatments that prevent nosocomial and cross-infections are essential for patients and dental workers. However, dental students sometimes pay inadequate attention to infection control, especially in preclinical practice, because of too much focus on technical training, such as the use of equipment, etc. The spread of infections such as SARS-CoV-2, antibiotic-resistant bacteria, and oral bacteria are sometimes lethal for medically compromised patients. Thus, the rapid and inexpensive detection system to detect and measure dental practice-related infection spread during preclinical treatment is highly desired for dental education. This study aimed to establish a method to quantify and visualize infected areas using dental phantoms for safe and effective preclinical dental practices. METHODS: At first, we developed artificial saliva as an in vitro study, including food-derived bacteria and fluorescence dye, which is safe for application to preclinical practice education. In vitro study, the correlation between adenosine triphosphate (ATP) levels and Lactobacillus colony numbers in yogurt was examined using the ATP fluorescent method, with colony counting on yogurt only and a mixture of yogurt and ultraviolet (UV)-sensitive hand lotion. The mixed liquid of yogurt and hand lotion was used as artificial saliva. Second, we used this artificial saliva in preclinical education. The degree of contamination of personal protective equipment and dental chairs in preclinical practice using this artificial saliva was determined using the ATP fluorescent method and measuring the luminescence areas among 10 dentists, 10 dental residents, and 10 fifth-grade dental students. RESULTS: ATP levels and Lactobacillus colony numbers in yogurt were positively correlated with yogurt alone and a mixture of yogurt and UV-sensitive hand lotions (correlation coefficient ≒ 1). Preclinical education using a mixture of artificial saliva successfully quantified and visualized infectious areas and droplets, which revealed significant differences in ATP amounts in personal protective equipment among groups according to years of experience as dental practitioners (p < 0.05). CONCLUSIONS: An education system for infection control constructed using artificial saliva containing Lactobacillus and a UV-sensitive fluorescent hand lotion quantified the infectious areas and degrees. Thus, this method is effective in preclinical practice using dental phantoms.

DOI： 10.1186/s12903-025-05584-4

PubMed

researchmap

Effectiveness of oral health care intervention for stroke patients following the introduction of Oral Health Assessment Tool. 査読

Kazuyuki Matsunaga, Ayaka Yoshida-Tsuboi, Ken Inohara, Yasuko Yoshida, Kanako Nakahama, Kazuki Sasaki, Fumie Souda, Yuka Terasawa, Yutaka Shimoe, Kazu Takeuchi-Hatanaka, Tadashi Yamamoto, Kazuhiro Omori, Tatsuo Kohriyama, Shogo Takashiba

Geriatrics & gerontology international   2024年12月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: This study aimed to evaluate the effectiveness of oral health assessment tools in facilitating oral health care interventions by dental care providers for acute stroke patients within 48 h of admission, following a reform of the nursing system. METHODS: Data were gathered from a retrospective cohort study conducted at a stroke center, comparing 10 months before and after the implementation of the reformed system, with a 2-month interval. Parameters assessed included stroke type, severity measured using the National Institutes of Health Stroke Scale, stroke history, stroke-related factors, number of teeth, hospitalization cost and duration, occurrence of fever and pneumonia, stroke treatment, days from admission to dental intervention, and intervention frequency. RESULTS: Implementation of the new system significantly reduced the time before dental intervention (P < 0.001), increased the frequency of interventions (P < 0.001), and allowed for the management of more severe cases (P = 0.007). However, there was a slight increase in the occurrence of fevers and the days of fever (P = 0.039 and P = 0.015, respectively). Multiple regression analysis showed that fever days were positively correlated with stroke severity and the number of days from admission to dental intervention (P < 0.001 and P = 0.013, respectively). Even after propensity score matching adjusting for stroke severity, these associations persisted. Additional multiple regression analysis was performed after this, but fever days were positively correlated with stroke severity and sex (P < 0.001 and P = 0.008, respectively), as well as with the presence of other factors affecting the occurrence of fever. CONCLUSIONS: Although the frequency and duration of fevers increased slightly, this approach, incorporating oral health assessment tools, made it possible to provide early dental intervention, particularly for patients with severe strokes. Geriatr Gerontol Int 2024; ••: ••-••.

DOI： 10.1111/ggi.15035

PubMed

researchmap

B-catenin binds to Gsk-3b in liquid-liquid phase separation compartment inHEK293 cells 査読

Kato M, Tanai A, Fukuhara Y, Zheng X, Sitosari H, Yamamoto T, Ikegami M, Okamura H

33 ( 4 )   213 - 218   2024年10月

　詳細を見る

掲載種別：研究論文（学術雑誌）  

researchmap

Resolvin D2-induced reparative dentin and pulp stem cells after pulpotomy in a rat model 査読

Mitsuhiro Yoneda, Hidetaka Ideguchi, Shin Nakamura, Zulema Arias, Mitsuaki Ono, Kazuhiro Omori, Tadashi Yamamoto, Shogo Takashiba

Heliyon   10 ( 13 )   e34206 - e34206   2024年7月

　詳細を見る

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.heliyon.2024.e34206

researchmap

Bacterial DNA and serum IgG antibody titer assays for assessing infection of human-pathogenic and dog-pathogenic Porphyromonas species in dogs 査読

Masako Tai-Tokuzen, Takashi Ito, Kazuya Tamura, Haruko Hirayama, Hirohito Ogawa, Shin Nakamura, Keisuke Okubo, Kazuhiro Omori, Tadashi Yamamoto, Katsumi Mominoki, Shogo Takashiba

Heliyon   10 ( 11 )   e31872 - e31872   2024年6月

　詳細を見る

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.heliyon.2024.e31872

researchmap

Ligneous periodontitis exacerbated by Behçet's disease in a patient with plasminogen deficiency and a stop-gained variant PLG c.1468C > T: a case report. 査読 国際誌

Yuki Shinoda-Ito, Anna Hirai, Kazuhiro Omori, Hidetaka Ideguchi, Hideki Yamamoto, Fumino Kato, Kyoichi Obata, Tatsuo Ogawa, Keisuke Nakano, Takato Nakadoi, Eri Katsuyama, Soichiro Ibaragi, Tadashi Yamamoto, Hitoshi Nagatsuka, Akira Hirasawa, Shogo Takashiba

BMC oral health   23 ( 1 )   843 - 843   2023年11月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity. CASE PRESENTATION: This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated. CONCLUSIONS: Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.

DOI： 10.1186/s12903-023-03586-8

PubMed

researchmap

歯内治療が原因で菌血症となった単心室症患者の一症例 査読

大森 一弘, 杜 徳尚, 井手口 英隆, 岡本 憲太郎, 佐光 秀文, 児玉 加奈子, 山本 直史, 赤木 禎治, 笠原 真悟, 伊藤 浩, 高柴 正悟

日本成人先天性心疾患学会雑誌   12 ( 2 )   30 - 36   2023年5月

　詳細を見る

記述言語：日本語   出版者・発行元：(一社)日本成人先天性心疾患学会  

歯科治療は,観血的処置にはみえなくても菌血症を起こすリスクが高い.今回,感染性心内膜炎(IE)高リスクに分類されるフォンタン手術後の患者が歯科治療に起因すると考えられる感染症を起こし,緊急入院に至る症例を経験した.患者は20歳の男性.多脾症候群,右室型単心室に対して,両側両方向性グレン手術とフォンタン手術の手術歴がある.2021年6月,近医で下顎左側第二大臼歯(#37)の慢性根尖性歯周炎の診断のもと,予防的抗菌薬の投与なく歯内治療を開始した.2021年7月,治療中の#37部の自発痛,悪寒,戦慄,発熱を自覚し,当院循環器内科を緊急受診した.履歴から歯性感染が疑われたため,当院歯周科へ緊急紹介され,#37急性根尖性歯周炎と診断した.IE高リスク患者のため緊急入院となり,経験的抗菌療法を開始した.入院5日目,抗菌薬持続投与下で#37の歯内治療を再開,入院12日目に歯内治療を終了,入院13日目に退院した.今回の症例を教訓に,患者自身が歯科治療に先立ち予防的抗菌薬投与の必要性を簡便に提示できる患者カードを作成した.本カードが適切に運用され,歯科治療由来のIE発症リスクが軽減されることを期待する.(著者抄録)

researchmap

Personalized Preclinical Training in Dental Ergonomics and Endodontics in Undergraduate Dentistry Students (Pilot Study). 査読

Zulema Arias, Stephanie Haines, Tadashi Yamamoto, Kazu Hatanaka, Keisuke Yamashiro, Norihiro Sonoi, Shogo Takashiba

Acta medica Okayama   77 ( 2 )   147 - 159   2023年4月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The curriculum at the Department of Pathophysiology in the Periodontal Sciences program at Okayama University includes normative preclinical training (NPT) using phantoms. NPT is given to the whole class of 5 th year students divided in groups of 8 students/instructor. In 2019, an innovative personalized preclinical training (PPT) pilot study was implemented for this group of students whereby two students, each with their own dental unit, were coached by one instructor. The main topics covered were dental ergonomics and endodontics. We aimed to evaluate the effectiveness of PPT in dental ergonomics and endodontics toward increasing the knowledge and future clinical skills of students who had already undergone NPT. A test on endodontics was taken before and after PPT. A questionnaire was completed to assess their perception of improvement regarding the above-mentioned topics. Test scores and questionnaire results both showed that the students' level of knowledge and awareness of future clinical skills was significantly higher after PPT. This pilot study demonstrated that PPT increased the students' knowledge and future clinical skills. As preclinical training forms the foundation for clinical practice, investment in future research regarding this personalized approach is likely to enhance students' understanding and clinical performance.

DOI： 10.18926/AMO/65144

PubMed

researchmap

The Fungal Metabolite (+)-Terrein Abrogates Inflammatory Bone Resorption via the Suppression of TNF-α Production in a Ligature-Induced Periodontitis Mouse Model 査読

Hidefumi Sako, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Hidetaka Ideguchi, Saki Yoshimura-Nakagawa, Kyosuke Sakaida, Chiaki Nagata-Kamei, Hiroya Kobayashi, Satoki Ishii, Mitsuaki Ono, Soichiro Ibaragi, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba

Journal of Fungi   9 ( 3 )   314 - 314   2023年3月

　詳細を見る

掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Current periodontal treatment focuses on the mechanical removal of the source of infection, such as bacteria and their products, and there is no approach to control the host inflammatory response that leads to tissue destruction. In order to control periodontal inflammation, we have previously reported the optimization of (+)-terrein synthesis methods and the inhibitory effect of (+)-terrein on osteoclast differentiation in vitro. However, the pharmacological effect of (+)-terrein in vivo in the periodontitis model is still unknown. In this study, we investigated the effect of synthetic (+)-terrein on inflammatory bone resorption using a ligature-induced periodontitis mouse model. Synthetic (+)-terrein (30 mg/kg) was administered intraperitoneally twice a week to the mouse periodontitis model. The control group was treated with phosphate buffer. One to two weeks after the induction of periodontitis, the periodontal tissues were harvested for radiological evaluation (micro-CT), histological evaluation (HE staining and TRAP staining), and the evaluation of inflammatory cytokine production in the periodontal tissues and serum (quantitative reverse-transcription PCR, ELISA). The synthetic (+)-terrein-treated group suppressed alveolar bone resorption and the number of osteoclasts in the periodontal tissues compared to the control group (p &lt; 0.05). In addition, synthetic (+)-terrein significantly suppressed both mRNA expression of TNF-α in the periodontal tissues and the serum concentration of TNF-α (both p &lt; 0.05). In conclusion, we have demonstrated that synthetic (+)-terrein abrogates alveolar bone resorption via the suppression of TNF-α production and osteoclast differentiation in vivo. Therefore, we could expect potential clinical effects when using (+)-terrein on inflammatory bone resorption, including periodontitis.

DOI： 10.3390/jof9030314

researchmap

患者自身が管理するPHRを活用した安全安心な歯科医療環境の構築 査読

高柴 正悟, 田上 順次, 齋藤 正寛, 高橋 慶壮, 横瀬 敏志, 細矢 哲康, 三谷 章雄, 山本 直史

日本歯科医学会誌(0286-164X)42巻 Page58-64(2023.03)   42   58 - 64   2023年3月

　詳細を見る

researchmap

Autophagy as a potential mechanism underlying the biological effect of 1,25-Dihydroxyvitamin D3 on periodontitis: a narrative review. 査読 国際誌

Xiaoting Chen, Zulema Arias, Kazuhiro Omori, Tadashi Yamamoto, Yuki Shinoda-Ito, Shogo Takashiba

BMC oral health   23 ( 1 )   90 - 90   2023年2月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The major active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is known for its wide bioactivity in periodontal tissues. Although the exact mechanisms underlying its protective action against periodontitis remain unclear, recent studies have shown that 1,25D3 regulates autophagy. Autophagy is vital for intracellular pathogen invasion control, inflammation regulation, and bone metabolic balance in periodontal tissue homeostasis, and its regulation could be an interesting pathway for future periodontal studies. Since vitamin D deficiency is a worldwide health problem, its role as a potential regulator of autophagy provides new insights into periodontal diseases. Based on this premise, this narrative literature review aimed to investigate the possible connection between 1,25D3 and autophagy in periodontitis. A comprehensive literature search was conducted on PubMed using the following keywords (e.g., vitamin D, autophagy, periodontitis, pathogens, epithelial cells, immunity, inflammation, and bone loss). In this review, the latest studies on the protective action of 1,25D3 against periodontitis and the regulation of autophagy by 1,25D3 are summarized, and the potential role of 1,25D3-activated autophagy in the pathogenesis of periodontitis is analyzed. 1,25D3 can exert a protective effect against periodontitis through different signaling pathways in the pathogenesis of periodontitis, and at least part of this regulatory effect is achieved through the activation of the autophagic response. This review will help clarify the relationship between 1,25D3 and autophagy in the homeostasis of periodontal tissues and provide perspectives for researchers to optimize prevention and treatment strategies in the future.

DOI： 10.1186/s12903-023-02802-9

PubMed

researchmap

歯内治療が原因で菌血症となった単心室症患者の一症例 査読

大森 一弘, 杜 徳尚, 井手口 英隆, 岡本 憲太郎, 佐光 秀文, 児玉 加奈子, 山本 直史, 赤木 禎治, 笠原 真悟, 伊藤 浩, 高柴 正悟

日本成人先天性心疾患学会雑誌   12 ( 2 )   1 - 8   2023年2月

　詳細を見る

DOI： 10.34376/jsachd.C-2022-0002

researchmap

Reattachment of Fractured Tooth Fragment by Multidisciplinary Treatment Approach 査読

Zulema Arias, Heber Falú Hinojosa Ledezma, Claudia Patricia Osorio Terán, Kazuhiro Omori, Tadashi Yamamoto, Mohammed Zahedul Islam Nizami, Shogo Takashiba

The Bulletin of Tokyo Dental College   2023年

　詳細を見る

掲載種別：研究論文（学術雑誌）   出版者・発行元：Tokyo Dental College  

DOI： 10.2209/tdcpublication.2022-0019

researchmap

Graphene Oxide-based Endodontic Sealer: An in Vitro Study. 査読

Mohammed Zahedul Islam Nizami, Melahat Gorduysus, Yuki Shinoda-Ito, Tadashi Yamamoto, Yuta Nishina, Shogo Takashiba, Zulema Arias

Acta medica Okayama   76 ( 6 )   715 - 721   2022年12月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The failure of endodontic treatment is directly associated with microbial infection in the root canal or periapical areas. An endodontic sealer that is both bactericidal and biocompatible is essential for the success of root canal treatments. This is one of the vital issues yet to be solved in clinical dental practice. This in vitro study assessed the effectiveness of graphene oxide (GO) composites GO-CaF2 and GO-Ag-CaF2 as endodontic sealer materials. Dentin slices were coated with either the GO-based composites or commonly used root canal sealers (non-eugenol zinc oxide sealer). The coated slices were treated in 0.9% NaCl, phosphate-buffered saline (PBS), and simulated body fluid (SBF) at 37˚C for 24 hours to compare their sealing effect on the dentin surface. In addition, the radiopacity of these composites was examined to assess whether they complied with the requirements of a sealer for good radiographic visualization. Scanning electron microscopy showed the significant sealing capability of the composites as coating materials. Radiographic images confirmed their radiopacity. Mineral deposition indicated their bioactivity, especially of GO-Ag-CaF2, and thus it is potential for regenerative application. They were both previously shown to be bactericidal to oral microbes and cytocompatible with host cells. With such a unique assemblage of critical properties, these GO-based composites show promise as endodontic sealers for protection against reinfection in root canal treatment and enhanced success in endodontic treatment overall.

DOI： 10.18926/AMO/64122

PubMed

researchmap

Treatment resistance of rheumatoid arthritis relates to infection of periodontal pathogenic bacteria: a case-control cross-sectional study. 査読 国際誌

Kazu Takeuchi-Hatanaka, Yoshinobu Koyama, Kentaro Okamoto, Kyosuke Sakaida, Tadashi Yamamoto, Shogo Takashiba

Scientific reports   12 ( 1 )   12353 - 12353   2022年7月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recent studies have shown that periodontitis is associated with rheumatoid arthritis (RA) and periodontal bacteria, such as Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are involved in the pathogenesis of RA via citrullinated proteins. Smoking has also been shown to be involved in the pathogenesis of RA; however, the extent of this involvement is still poorly understood. In addition, RA and polymyalgia rheumatica (PMR) are sometimes difficult to differentiate; however, the relationship between PMR and the factors from smoking and periodontal bacteria is unclear. The aim of this study was to clarify the relationship between periodontal pathogenic bacterial infections and smoking in patients with RA or PMR. This case-control study included 142 patients with untreated RA or PMR. This study evaluated the serum antibody titers against periodontal pathogenic bacterial antigens and an anti-citrullinated peptide antibody (ACPA). In patients with RA, the relationship between antibody titers and disease activity of RA and response after 3 months of treatment was also investigated. Additionally, the effects of smoking were evaluated. Although there was no significant difference in serum antibody titer against periodontal pathogenic bacteria between the ACPA-positive RA group and the ACPA-negative PMR group, we found an association between the elevated antibody titer against Pg and the degree of ACPA value, especially between negative group and high-value positive group (≥ 100 U/mL). The antibody titers against Aa and Pg did not differ depending on disease activity score 28 (DAS28) at baseline; however, patients with high antibody titers had poor RA therapeutic response as judged by DAS28 after 3 months. We could not find any association between smoking and any of these parameters. Periodontal pathogenic bacteria, especially Pg, are associated with elevated ACPA levels. Our findings suggest that Pg and Aa infections interfere with the therapeutic response of RA.

DOI： 10.1038/s41598-022-16279-z

PubMed

researchmap

Analysis of subgingival microbiota in monozygotic twins with different severity and progression risk of periodontitis. 査読 国際誌

Tadashi Yamamoto, Makoto Taniguchi, Kazuyuki Matsunaga, Yusuke Kawata, Mari Kawamura, Keisuke Okubo, Keisuke Yamashiro, Kazuhiro Omori, Shogo Takashiba

Clinical case reports   10 ( 4 )   e05725   2022年4月

　詳細を見る

担当区分：筆頭著者,　責任著者   記述言語：英語  

The study aims to reveal the composition of subgingival bacteria in monozygotic twins with discordant in severity and progression risk of periodontitis. Microbiome analysis indicated that most bacteria were heritable but differed in their abundance and immune response. The dysbiotic bacteria can be considered as risk markers for periodontitis progression.

DOI： 10.1002/ccr3.5725

PubMed

researchmap

Estimation of periodontal pocket surface area in small to medium dogs: a proof-of-concept study. 査読 国際誌

Kazuya Tamura, Masako Tokuzen-Tai, Yasir Dilshad Siddiqui, Hitomi Tamura-Naito, Yoshiharu Nagahara, Kazu Hatanaka-Takeuchi, Tadashi Yamamoto, Shogo Takashiba

BMC veterinary research   18 ( 1 )   13 - 13   2022年1月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Periodontal disease is the most common dental disease in dogs. Although the systemic effects of periodontal disease have not been clarified in veterinary science, it is necessary to evaluate the effects of periodontal disease in clinical trials in the future. There have been a few clinical attempts made, however, to assess the severity of periodontal inflammation and its impact on the systemic health of dogs. Meanwhile, in the field of dentistry for humans, the periodontal inflamed surface area (PISA) and periodontal epithelial surface area (PESA) have been used to quantitatively assess the degree of periodontal disease affecting a single tooth as well as the overall extent of periodontitis. Recent studies have also suggested the use of these assessments to examine the relationship between periodontal inflammation and systemic health. RESULTS: The estimation formula for a dog's periodontal pocket surface area (PPSA), an alternative to PISA and PESA in humans, was established using body weight and periodontal pocket depth. Actual values were measured using extracted teeth from various dog breeds and sizes (2.3-25.0 kg of body weight) to obtain universal regression equations for PPSA. Altogether, 625 teeth from 73 dogs of 16 breeds were extracted and subsequently analyzed for morphological information. PPSA was measured in 61 dogs of 10 breeds with periodontal disease using the established estimation formulas, and the correlation between PPSA and preoperative blood chemistry data was analyzed accordingly. A strong correlation was found between PPSA and serum globulin (r = 0.71) while moderate correlations were found for C-reactive protein (r = 0.54) and serum albumin (r = -0.51). CONCLUSIONS: Estimation formulas using body weight and the 6-point probing depth were established for determining PPSA. Direct correlations between PPSA and several blood test results were observed in the study sample. Taken together, these results suggest that PPSA could be useful for evaluating the effects of periodontitis on systemic conditions in dogs.

DOI： 10.1186/s12917-021-03116-0

PubMed

researchmap

Enzymatic measurement of short-chain fatty acids and application in periodontal disease diagnosis. 査読 国際誌

Kazu Hatanaka, Yasushi Shirahase, Toshiyuki Yoshida, Mari Kono, Naoki Toya, Shin-Ichi Sakasegawa, Kenji Konishi, Tadashi Yamamoto, Kuniyasu Ochiai, Shogo Takashiba

PloS one   17 ( 7 )   e0268671   2022年

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Periodontal disease is a chronic inflammatory condition caused by periodontal pathogens in the gingival sulcus. Short-chain fatty acids (SCFAs) produced by causal bacteria are closely related to the onset and progression of periodontal disease and have been reported to proliferate in the periodontal sulcus of patients experiencing this pathology. In such patients, propionic acid (C3), butyric acid (C4), isobutyric acid (IC4), valeric acid (C5), isovaleric acid (IC5), and caproic acid (C6), henceforth referred to as [C3-C6], has been reported to have a detrimental effect, while acetic acid (C2) exhibits no detrimental effect. In this study, we established an inexpensive and simple enzymatic assay that can fractionate and measure these acids. The possibility of applying this technique to determine the severity of periodontal disease by adapting it to specimens collected from humans has been explored. We established an enzyme system using acetate kinase and butyrate kinase capable of measuring SCFAs in two fractions, C2 and [C3-C6]. The gingival crevicular fluid (GCF) and saliva of 10 healthy participants and 10 participants with mild and severe periodontal disease were measured using the established enzymatic method and conventional gas chromatography-mass spectrometry (GC-MS). The quantification of C2 and [C3-C6] in human GCF and saliva was well correlated when using the GC-MS method. Furthermore, both C2 and [C3-C6] in the GCF increased with disease severity. However, while no significant difference was observed between healthy participants and periodontal patients when using saliva, [C3-C6] significantly differed between mild and severe periodontal disease. The enzymatic method was able to measure C2 and [C3-C6] separately as well as using the GC-MS method. Furthermore, the C2 and [C3-C6] fractions of GCF correlated with disease severity, suggesting that this method can be applied clinically. In contrast, the quantification of C2 and [C3-C6] in saliva did not differ significantly between healthy participants and patients with periodontal disease. Future studies should focus on inflammation rather than on tissue destruction.

DOI： 10.1371/journal.pone.0268671

PubMed

researchmap

Malnutrition delayed wound healing after tooth extraction by HMGB1-related prolonged inflammation. 査読 国際誌

Yao Zhang, Hidetaka Ideguchi, Hiroaki Aoyagi, Keisuke Yamashiro, Tadashi Yamamoto, Masahiro Nishibori, Shogo Takashiba

International immunopharmacology   96   107772 - 107772   2021年7月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Malnutrition causes prolonged inflammation, resulting in delayed wound healing. High mobility group box-1 (HMGB1) is a damage-associated molecular pattern that is present in the nuclei of macrophages and is secreted into the extracellular milieu in response to stimuli. It stimulates the production of interleukin-1β (IL-1β) through the receptors for advanced glycation end products (RAGE), inducing an inflammatory response, which is an essential response to initiate wound healing. We hypothesized that malnutrition may interfere with this cascade, causing abnormal inflammation and ultimately delaying wound healing. We used tooth-extracted mice with malnutrition fed with low-casein diet for two weeks. On days 3 and 7 after tooth extraction, the wound tissue was histologically observed and analyzed for several factors in the inflammation-regeneration lineage, including IL-1β, mesenchymal stem cells, myeloperoxidase activity, HMGB1, macrophage polarization, and adenosine 5-triphosphate (ATP). On day 7, delayed wound healing was observed with the following findings under malnutrition conditions: decreased mRNA expression of genes for regeneration and mesenchymal stem cell (MSC) accumulation, an obvious increase in myeloperoxidase and IL-1β mRNA expression, an increase in HMGB1 levels, and an increase in ATP concentration in tissues with elevated proportion of M2 macrophages. These results suggest that the significantly increased secretion of HMGB1 associated with the upregulated production of ATP and IL-1β secretion via the RAGE pathway may interfere with the resolution of inflammation and wound healing under the state of malnutrition.

DOI： 10.1016/j.intimp.2021.107772

PubMed

researchmap

The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C α/βII Phosphorylation. 査読 国際誌

Kyosuke Sakaida, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Saki Nakagawa, Hidefumi Sako, Chiaki Kamei, Satoshi Yamamoto, Hiroya Kobayashi, Satoki Ishii, Mitsuaki Ono, Soichiro Ibaragi, Keisuke Yamashiro, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba

Frontiers in pharmacology   12   674366 - 674366   2021年

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKCα/βII, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis.

DOI： 10.3389/fphar.2021.674366

PubMed

researchmap

Use of Highly Accurate Devices for a First Lower Premolar Endodontic Treatment with Multiple Root Canals. 査読

Zulema Arias Martinez, Jorge Lopez Videla, Keisuke Yamashiro, Yuki Shinoda-Ito, Tadashi Yamamoto, Shogo Takashiba

Acta medica Okayama   75 ( 5 )   641 - 645   2021年

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

This case report highlights the importance of using a dental operating microscope (DOM) and ultrasonic endodontic tips (UETs) to locate all root canals in the lower first premolar. A 53-year-old woman presented to our clinic with pain in the lower right first premolar. After a detailed search using a DOM and UETs, three root canals were found, prepared with rotary HyFlex endodontic files, and obturated using the lateral condensation technique. At the five-year follow-up after treatment, the tooth was completely restored and fulfilling its function, with no signs or symptoms of any post-treatment flare-up.

DOI： 10.18926/AMO/62778

PubMed

researchmap

Follistatin expressed in mechanically-damaged salivary glands of male mice induces proliferation of CD49f+ cells 査読

A. Ikeda, T. Yamamoto, J. Mineshiba, S. Takashiba

Scientific Reports   10 ( 1 )   2020年12月

　詳細を見る

掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

<title>Abstract</title>Salivary glands (SGs) are very important for maintaining the physiological functions of the mouth. When SGs regenerate and repair from various damages, including mechanical, radiological, and immune diseases, acinar and granular duct cells originate from intercalated duct cells. However, the recovery is often insufficient because of SGs' limited self-repair function. Furthermore, the precise repair mechanism has been unclear. Here, we focused on CD49f, one of the putative stem cell markers, and characterized CD49f positive cells (CD49f⁺ cells) isolated from male murine SGs. CD49f⁺ cells possess self-renewal ability and express epithelial and pluripotent markers. Compared to CD49f negative cells, freshly isolated CD49f⁺ cells highly expressed inhibin beta A and beta B, which are components of activin that has anti-proliferative effects. Notably, an inhibitor of activin, follistatin was expressed in mechanically-damaged SGs, meanwhile no follistatin was expressed in normal SGs in vivo. Moreover, sub-cultured CD49f⁺ cells highly expressed both <italic>Follistatin</italic> and a series of proliferative genes, expressions of which were decreased by <italic>Follistatin</italic> siRNA. These findings indicated that the molecular interaction between activin and follistatin may induce CD49f⁺ cells proliferation in the regeneration and repair of mouse SGs.

DOI： 10.1038/s41598-020-77004-2

researchmap

その他リンク： http://www.nature.com/articles/s41598-020-77004-2

歯周組織の炎症と不妊の関連性を示唆する、ある侵襲性歯周炎患者の病態生理 査読

大森 一弘, 河野 隆幸, 小林 寛也, 新井 英雄, 山本 直史, 高柴 正悟

日本歯科保存学雑誌   63 ( 5 )   451 - 460   2020年10月

　詳細を見る

記述言語：日本語   出版者・発行元：(NPO)日本歯科保存学会  

緒言:歯周病原細菌の感染と歯周組織の炎症が,妊娠に影響を与える可能性が報告されている.今回,不妊治療の経過が思わしくない侵襲性歯周炎患者に感染源除去の観点から専門的歯周治療を行い,自然妊娠から正常出産にいたった症例の経過をふまえ病態を考察する.症例:33歳,女性,既婚(不妊治療中).2016年9月,26の動揺および同部の自発痛を自覚し,かかりつけ歯科医院を受診した.同院でエックス線検査を受けて,重度の歯槽骨吸収があると説明された.早期の専門的歯周治療を勧められ,当科を紹介された.既往歴の特記事項はなく,不妊検査においても患者本人および夫ともに異常所見はなかった.歯周組織検査において,probing pocket depthが4mm以上の部位の割合は49.5%,bleeding on probingは47.9%,plaque control recordは3.1%,歯周炎症表面積(PISA)は2,392mm2であった.エックス線検査所見では,主訴部の26部を中心に根尖に及ぶ骨吸収像が多数存在した.歯周病原細菌に対する血清抗体価検査および歯周ポケット内細菌DNA検査ともに,Porphyromonas gingivalisの感染が強く疑われた.診断は広汎型侵襲性歯周炎(ステージIV,グレードC),二次性咬合性外傷とした.治療方針として,患者の妊娠希望に配慮して,できるかぎり早期(1年以内)の歯周環境の改善を目指すこととした.また,歯周外科治療が終了するまでの不妊治療を含めた妊娠活動を控える必要性について説明し,同意を得た.治療計画は,(1)歯周基本治療(患者教育,抜歯,局所抗菌療法を併用したスケーリング・ルートプレーニング,暫間固定),(2)歯周組織再生療法,(3)口腔機能回復治療,(4)歯周病安定期治療(SPT)とした.治療経過として,歯周治療に対する宿主反応性は非常に良く,炎症改善と歯槽骨の再生を確認した(歯周外科治療後PISA:43mm2).口腔機能回復治療中に自然妊娠し,35歳時に男児を正常出産(経腟分娩,3,240g,出産週数:38週+5日)した.考察および結論:重度のP. gingivalis感染および歯周炎症を伴う侵襲性歯周炎の罹患が,妊娠成立に影響を及ぼす可能性が示唆された.本症例のように不妊治療の経過が思わしくない場合には,歯周組織を含めた口腔状態を一度精査することが望まれる.(著者抄録)

researchmap

Isolation and identification of the antimicrobial substance included in tempeh using Rhizopus stolonifer NBRC 30816 for fermentation. 査読 国際誌

Masahiro Ito, Takashi Ito, Hideyuki Aoki, Koshi Nishioka, Tsugumi Shiokawa, Hiroko Tada, Yuki Takeuchi, Nobuyuki Takeyasu, Tadashi Yamamoto, Shogo Takashiba

International journal of food microbiology   325   108645 - 108645   2020年7月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In this study, we focus on the antimicrobial properties of tempeh, a soybean fermented food, against oral bacteria. Tempeh showed antimicrobial activity against dental caries pathogenic bacterium Streptococcus mutans at a final concentration of 1 mg/mL. An antimicrobial substance contained in tempeh was present in the 100 kDa or greater fraction generated by ultrafiltration, but it was found not to be proteinaceous by native-PAGE, SDS-PAGE and protein degradation tests. Next, when the fraction was purified with an ODS column, the 80% and 100% methanol eluates showed antimicrobial activity against S. mutans. The 100% methanol eluate was further subjected to a 2nd column purification, and isolation of the target was confirmed by HPLC. When the isolated material was analyzed by ESI-MS, the m/z was 279.234. Further analysis by Raman spectroscopy revealed a peak similar to linoleic acid. This substance also possessed antimicrobial properties equivalent to linoleic acid.

DOI： 10.1016/j.ijfoodmicro.2020.108645

Scopus

PubMed

researchmap

The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1. 査読 国際誌

Saki Nakagawa, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Satoshi Yamamoto, Hiroya Kobayashi, Hidefumi Sako, Kyosuke Sakaida, Hiroshi Yoshimura, Satoki Ishii, Soichiro Ibaragi, Kimito Hirai, Keisuke Yamashiro, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba

International immunopharmacology   83   106429 - 106429   2020年6月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease.

DOI： 10.1016/j.intimp.2020.106429

Scopus

PubMed

researchmap

Evaluation of the simulator with automatic irrigation control system designed for countermeasures of internal contamination in dental unit water lines. 査読 国際誌

Keisuke Okubo, Takashi Ito, Kentaro Okamoto, Ichiro Yamamoto, Hajime Mizutani, Yusuke Kawata, Yasuyoshi Shiota, Masahiro Ito, Shin Nakamura, Masako Tai, Tadashi Yamamoto, Shogo Takashiba

Heliyon   6 ( 6 )   e04132   2020年6月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The prevention of nosocomial infections is an imperative task. The dental chair unit (DCU) is an indispensable device used in dental treatment. However, it is known that the dental unit water line (DUWL) can become contaminated with biofilm, consisting mainly of heterotrophic bacteria (HB). Recently, the International Organization for Standardization specified the methods for testing DUWL contamination management. On these grounds, a simulator reproducing DUWL was prepared to standardize the examination method of the DUWL contamination. Objectives: To evaluate the reproducibility of the DUWL simulator, monitor the DUWL contamination states, and test the efficacy of a commercial decontaminant for DUWL. Methods: The DUWL simulator was assembled by a DCU manufacturing company. The simulator's DUWL was filled with tap water (TW), and left for approximately one year. Neutral electrolyzed water (NEW) was used as a decontaminant for DUWL. Both TW and NEW were passed through DUWL in a timely manner simulating daily dental treatment. Water was sampled from the air turbine hand piece weekly for 4 weeks and used for HB culture. Contamination status was evaluated by measuring bacterial adenosine triphosphate release and by culturing on Reasoner's 2A medium. Results: The DUWL released contaminated water had a bacterial count of over 6 × 104 cfu/mL. After passing NEW through DUWL for 1 week, the count drastically decreased to its basal level and remained steady for 4 weeks. However, TW showed no effect on DUWL decontamination throughout the examination periods. Conclusions: The DUWL simulator could be useful to examine the efficacy of the decontaminant for DUWL and development of new methods in DUWL contamination management.

DOI： 10.1016/j.heliyon.2020.e04132

Scopus

PubMed

researchmap

Functionalized Graphene Oxide Shields Tooth Dentin from Decalcification 査読

M. Z.I. Nizami, Y. Nishina, T. Yamamoto, Y. Shinoda-Ito, S. Takashiba

Journal of Dental Research   99 ( 2 )   182 - 188   2020年2月

　詳細を見る

掲載種別：研究論文（学術雑誌）  

© International & American Associations for Dental Research 2019. This in vitro study assessed the efficacy of functionalized graphene oxide (f-GO) nanocomposites on the decalcification of dentin, because dental caries of the root surface is becoming one of the new problems in aged society. Hydroxyapatite plates (HAP) and dentin slices were coated with f-GO nanocomposites by comparing them to silver diamine fluoride as a positive control, then treated with decalcification solutions such as ethylenediaminetetraacetic acid and citrate at 37°C for 24 h. Scanning electron microscopy (SEM) revealed significant protection of the surface morphology of HAP and dentin. On the other hand, a cariogenic Streptococcus mutans growth was inhibited by f-GO nanocomposites. In addition, cytotoxicity of them to epithelial cells was much less than that of povidone-iodine, which is commonly used for oral disinfectant. We synthesized 5 different f-GO nanocomposites such as GO–silver (Ag), GO-Ag–calcium fluoride (CaF2), GO-CaF2, GO-zinc, and GO–tricalcium phosphate (Ca3(PO4)2). They were standardized by evaluating under SEM, transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetry analysis (TGA), and Raman spectra after being synthesized in an aseptic technique. The abilities of GO-Ag, GO-Ag-CaF2, and GO-CaF2 nanocomposites were most preventive for decalcification. In addition, GO-Ag and GO-Ag-CaF2 almost completely inhibited S. mutans growth. However, they did not exhibit cytotoxicity to epithelial cells except at the highest concentration (0.1 w/v%) of GO-Ag and GO-Ag-CaF2. Furthermore, these f-GO nanocomposites exhibited less or no discoloration of dentin, although commonly used silver diamine fluoride causes discoloration of dentin to black. Thus, these f-GO nanocomposites are useful to protect dental caries on the tooth root that becomes a social problem in aged society.

DOI： 10.1177/0022034519894583

Scopus

PubMed

researchmap

Induction of migration of periodontal ligament cells by selective regulation of integrin subunits 査読

Mari Kawamura, Tadashi Yamamoto, Keisuke Yamashiro, Shinsuke Kochi, Chiaki Yoshihara-Hirata, Hidetaka Ideguchi, Hiroaki Aoyagi, Kazuhiro Omori, Shogo Takashiba

Journal of Cellular and Molecular Medicine   23 ( 2 )   1211 - 1223   2020年2月

　詳細を見る

担当区分：責任著者   掲載種別：研究論文（学術雑誌）  

© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. The recruitment of tissue-resident stem cells is important for wound regeneration. Periodontal ligament cells (PDL cells) are heterogeneous cell populations with stemness features that migrate into wound sites to regenerate periodontal fibres and neighbouring hard tissues. Cell migration is regulated by the local microenvironment, coordinated by growth factors and the extracellular matrix (ECM). Integrin-mediated cell adhesion to the ECM provides essential signals for migration. We hypothesized that PDL cell migration could be enhanced by selective expression of integrins. The migration of primary cultured PDL cells was induced by platelet-derived growth factor-BB (PDGF-BB). The effects of blocking specific integrins on migration and ECM adhesion were investigated based on the integrin expression profiles observed during migration. Up-regulation of integrins α3, α5, and fibronectin was identified at distinct localizations in migrating PDL cells. Treatment with anti-integrin α5 antibodies inhibited PDL cell migration. Treatment with anti-integrin α3, α3-blocking peptide, and α3 siRNA significantly enhanced cell migration, comparable to treatment with PDGF-BB. Furthermore, integrin α3 inhibition preferentially enhanced adhesion to fibronectin via integrin α5. These findings indicate that PDL cell migration is reciprocally regulated by integrin α3-mediated inhibition and α5-mediated promotion. Thus, targeting integrin expression is a possible therapeutic strategy for periodontal regeneration.

DOI： 10.1111/jcmm.14023

Scopus

PubMed

researchmap

Antimicrobial and antibiofilm effects of abietic acid on cariogenic Streptococcus mutans. 査読

Yuki Ito, Takashi Ito, Keisuke Yamashiro, Fumi Mineshiba, Kimito Hirai, Kazuhiro Omori, Tadashi Yamamoto, Shogo Takashiba

Odontology   108 ( 1 )   57 - 65   2020年1月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Dental caries is a type of oral microbiome dysbiosis and biofilm infection that affects oral and systemic conditions. For healthy life expectancy, natural bacteriostatic products are ideal for daily and lifetime use as anti-oral infection agents. This study aimed to evaluate the inhibitory effects of abietic acid, a diterpene derived from pine rosin, on the in vitro growth of cariogenic bacterial species, Streptococcus mutans. The effective minimum inhibitory concentration of abietic acid was determined through observation of S. mutans growth, acidification, and biofilm formation. The inhibitory effects of abietic acid on the bacterial membrane were investigated through the use of in situ viability analysis and scanning electron microscopic analysis. Cytotoxicity of abietic acid was also examined in the context of several human cell lines using tetrazolium reduction assay. Abietic acid was found to inhibit key bacterial growth hallmarks such as colony forming ability, adenosine triphosphate activity (both planktonic and biofilm), acid production, and biofilm formation. Abietic acid was identified as bacteriostatic, and this compound caused minimal damage to the bacterial membrane. This action was different from that of povidone-iodine or cetylpyridinium chloride. Additionally, abietic acid was significantly less cytotoxic compared to povidone-iodine, and it exerted lower toxicity towards epithelial cells and fibroblasts compared to that against monocytic cells. These data suggest that abietic acid may prove useful as an antibacterial and antibiofilm agent for controlling S. mutans infection.

DOI： 10.1007/s10266-019-00456-0

Scopus

PubMed

researchmap

Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis 査読

Daichi Isoshima, Keisuke Yamashiro, Kazuyuki Matsunaga, Makoto Taniguchi, Takehiro Matsubara, Shuta Tomida, Shinzo Ota, Michiyoshi Sato, Yutaka Shimoe, Tatsuo Kohriyama, Zulema Arias, Kazuhiro Omori, Tadashi Yamamoto, Shogo Takashiba

Odontology   2020年

　詳細を見る

掲載種別：研究論文（学術雑誌）  

© 2020, The Society of The Nippon Dental University. There is no conclusive evidence regarding a causal relationship between periodontitis and atherosclerosis. In this study, we examined the microbiome in the oral cavity and atheromatous plaques from atherosclerosis patients with or without periodontitis to investigate the role of oral bacteria in the formation of atheromatous plaques. We chose four patients with and without periodontitis, who had undergone carotid endarterectomy. Bacterial samples were extracted from the tongue surface, from periodontal pocket (during the oral examination), and from the atheromatous plaques (APs). We investigated the general and oral conditions from each patient and performed next-generation sequencing (NGS) analysis for all bacterial samples. There were no significant differences between both groups concerning general conditions. However, the microbiome patterns of the gingival pocket showed differences depending on the absence or presence of periodontitis, while those of the tongue surface were relatively similar. The microbiome pattern of the atheromatous plaques was entirely different from that on the tongue surface and gingival pocket, and oral bacteria were seldom detected. However, the microbiome pattern in atheromatous plaques was different in the presence or absence of periodontitis. These results suggested that oral bacteria did not affect the formation of atheromatous plaques directly.

DOI： 10.1007/s10266-020-00524-w

Scopus

researchmap

High Mobility Group Box 1 Expression in Oral Inflammation and Regeneration. 査読 国際誌

Keisuke Yamashiro, Hidetaka Ideguchi, Hiroaki Aoyagi, Chiaki Yoshihara-Hirata, Anna Hirai, Risa Suzuki-Kyoshima, Yao Zhang, Hidenori Wake, Masahiro Nishibori, Tadashi Yamamoto, Shogo Takashiba

Frontiers in immunology   11   1461 - 1461   2020年

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein of about 30 kDa. It is released from a variety of cells into the extracellular milieu in response to inflammatory stimuli and acts on specific cell-surface receptors, such as receptors for advanced glycation end-products (RAGE), Toll-like receptor (TLR)2, TLR4, with or without forming a complex with other molecules. HMGB1 mediates various mechanisms such as inflammation, cell migration, proliferation, and differentiation. On the other hand, HMGB1 enhances chemotaxis acting through the C-X-C motif chemokine ligand (CXCL)12/C-X-C chemokine receptor (CXCR)4 axis and is involved in regeneration. In the oral cavity, high levels of HMGB1 have been detected in the gingival tissue from periodontitis and peri-implantitis patients, and it has been shown that secreted HMGB1 induces pro-inflammatory cytokine expression, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, which prolong inflammation. In contrast, wound healing after tooth extraction or titanium dental implant osseointegration requires an initial acute inflammation, which is regulated by secreted HMGB1. This indicates that secreted HMGB1 regulates angiogenesis and bone remodeling by osteoclast and osteoblast activation and promotes bone healing in oral tissue repair. Therefore, HMGB1 can prolong inflammation in the periodontal tissue and, conversely, can regenerate or repair damaged tissues in the oral cavity. In this review, we highlight the role of HMGB1 in the oral cavity by comparing its function and regulation with its function in other diseases. We also discuss the necessity for further studies in this field to provide more specific scientific evidence for dentistry.

DOI： 10.3389/fimmu.2020.01461

Scopus

PubMed

researchmap

Acceleration of bone regeneration of horizontal bone defect in rats using collagen-binding basic fibroblast growth factor combined with collagen scaffolds 査読 国際誌

Shin Nakamura, Takashi Ito, Kentaro Okamoto, Takehiko Mima, Kentaro Uchida, Yasir D. Siddiqui, Masahiro Ito, Masako Tai, Keisuke Okubo, Keisuke Yamashiro, Kazuhiro Omori, Tadashi Yamamoto, Osamu Matsushita, Shogo Takashiba

Journal of Periodontology   90 ( 9 )   1043 - 1052   2019年9月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2019 The Authors. Journal of Periodontology published by Wiley Periodicals, Inc. on behalf of American Academy of Periodontology Background: Basic fibroblast growth factor (bFGF) has been applied for periodontal regeneration. However, the application depends on bone defect morphology because bFGF diffuses rapidly from defect sites. In a previous study, collagen-binding bFGF (CB-bFGF) has been shown to enhance bone formation by collagen-anchoring in the orthopedic field. The aim of this study is to demonstrate the efficacy of CB-bFGF with collagen scaffolds in bone regeneration of horizontal bone defect. Methods: Cell proliferation activity and collagen binding activity of CB-bFGF was confirmed by WST-8 assay and collagen binding assay, respectively. The retention of CB-bFGF in the collagen sheet (CS) was measured by fluorescence imaging. The rat horizontal alveolar bone defect model was employed to investigate the efficacy of CB-bFGF with collagen powder (CP). After 4 and 8 weeks, the regenerative efficacy was evaluated by microcomputed tomography, histological, and immunohistochemical analyses. Results: CB-bFGF had a comparable proliferation activity to bFGF and a collagen binding activity. CB-bFGF was retained in CS longer than bFGF. At 8 weeks postoperation, bone volume, bone mineral content, and new bone area in CB-bFGF/CP group were significantly increased compared with those in other groups. Furthermore, epithelial downgrowth was significantly suppressed in CB-bFGF/CP group. At 4 weeks, the numbers of osteocalcin, proliferating cell nuclear antigen, and osteopontin-positive cells at the regeneration site in CB-bFGF/CP group were greater than those in other groups. Conclusions: CB-bFGF/CP effectively promoted bone regeneration of horizontal bone defect possibly by sustained release of bFGF. The potential of CB-bFGF composite material for improved periodontal regeneration in vertical axis was shown.

DOI： 10.1002/JPER.18-0674

Scopus

PubMed

researchmap

Effectiveness and safety of low-concentrated ozonized water for the reduction of contamination in dental unit water lines. 査読 国際誌

Keisuke Okubo, Takashi Ito, Yasuyoshi Shiota, Yusuke Kawata, Tadashi Yamamoto, Shogo Takashiba

Heliyon   5 ( 8 )   e02306   2019年8月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Contamination of dental unit waterlines (DUWL) with heterotrophic bacteria can cause problems in immune compromised patients (aged, tumor and organ transplantation-patients). We focused on the use of low-concentrated ozonized water (OZW) as the biofilm formation restraint system for DUWL. Here, we examined the effects of low-concentrated OZW on the growth of bacteria and related biofilm formation and harmfulness to dental unit components (DUCs) in vitro. Objectives: To evaluate the bactericidal effects of OZW on biofilms in DUWL and DUC in vitro. Methods: Low-concentrated OZW (0.4 mg/L) was generated using an OZS-PTDX generator. Heterotrophic bacterial biofilms in old DUWL tubes and Candia albicans solution (control microbe) were treated with OZW for 1 h with gentle agitation before static culturing for 96 h in Reasoner's 2A liquid media. The control solutions were 0.1% cetylpyridinium chloride (CPC), chlorinated tap water (TW), and phosphate-buffered saline (PBS). Adenosine triphosphate (ATP) amounts of the microbes were measured and the biofilms of these microbes were observed using scanning electron microscopy (SEM). Moreover, surfaces of DUC soaked in OZW and TW were observed by SEM. Results: The OZW reduced ATP levels in microbes to 50% compared to TW and PBS treatment, although CPC reduced it below detection limits. SEM observation revealed deformation of microbes cultured with OZW, whereas no changes were seen on DUC surfaces. Conclusions: Low-concentrated OZW is bactericidal against heterotrophic bacteria biofilms and it is not harmful to DUC, suggesting that it might be useful in preventing DUWL contamination.

DOI： 10.1016/j.heliyon.2019.e02306

Scopus

PubMed

researchmap

Molecular imaging assessment of periodontitis lesions in an experimental mouse model 査読

Hidetaka Ideguchi, Keisuke Yamashiro, Tadashi Yamamoto, Masayuki Shimoe, Shoichi Hongo, Shinsuke Kochi, Chiaki Yoshihara-Hirata, Hiroaki Aoyagi, Mari Kawamura, Shogo Takashiba

Clinical Oral Investigations   23 ( 2 )   821 - 827   2019年2月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Verlag  

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Objective: We aimed to evaluate molecular imaging as a novel diagnostic tool for mice periodontitis model induced by ligature and Porphyromonas gingivalis (Pg) inoculation. Materials and methods: Twelve female mice were assigned to the following groups: no treatment as control group (n = 4); periodontitis group induced by ligature and Pg as Pg group (n = 4); and Pg group treated with glycyrrhizinic acid (GA) as Pg + GA group (n = 4). All mice were administered a myeloperoxidase (MPO) activity-specific luminescent probe and observed using a charge-coupled device camera on day 14. Image analysis on all mice was conducted using software to determine the signal intensity of inflammation. Additionally, histological and radiographic evaluation for periodontal inflammation and bone resorption at the site of periodontitis, and quantitative enzyme-linked immunosorbent assay (ELISA) were conducted on three mice for each group. Each experiment was performed three times. Results: Levels of serum IgG antibody against P. gingivalis were significantly higher in the Pg than in the Pg + GA group. Histological analyses indicated that the number of osteoclasts and neutrophils were significantly lower in the Pg + GA than in the Pg group. Micro-CT image analysis indicated no difference in bone resorption between the Pg and Pg + GA groups. The signal intensity of MPO activity was detected on the complete craniofacial image; moreover, strong signal intensity was localized specifically at the periodontitis site in the ex vivo palate, with group-wise differences. Conclusions: Molecular imaging analysis based on MPO activity showed high sensitivity of detection of periodontal inflammation in mice. Clinical relevance: Molecular imaging analysis based on MPO activity has potential as a diagnostic tool for periodontitis.

DOI： 10.1007/s00784-018-2510-2

Scopus

PubMed

researchmap

Resolvin D2 induces resolution of periapical inflammation and promotes healing of periapical lesions in rat periapical periodotitis 査読

Yasir Dilshad Siddiqui, Kazuhiro Omori, Takashi Ito, Keisuke Yamashiro, Shin Nakamura, Kentaro Okamoto, Mitsuaki Ono, Tadashi Yamamoto, Thomas E.Van Dyke, Shogo Takashiba

Frontiers in Immunology   10 ( FEB )   307   2019年

　詳細を見る

掲載種別：研究論文（学術雑誌）  

© 2019 Frew. Periapical periodontitis results from pulpal infection leading to pulpal necrosis and resorption of periapical bone. The current treatment is root canal therapy, which attempts to eliminate infection and necrotic tissue. But, in some cases periapical inflammation doesn't resolve even after treatment. Resolvins belongs to a large family of specialized pro-resolving lipid mediators that actively resolves inflammation signaling via specific receptors. Resolvin D2 (RvD2), a metabolite of docosahexaenoic acid (DHA), was tested as an intracanal medicament in rats in vivo. Mechanism was evaluated in rat primary dental pulp cells (DPCs) in vitro. The results demonstrate that RvD2 reduces inflammatory cell infiltrate, periapical lesion size, and fosters pulp like tissue regeneration and healing of periapical lesion. RvD2 enhanced expression of its receptor, GPR18, dentin matrix acidic phosphoprotein 1 (DMP1) and mineralization in vivo and in vitro. Moreover, RvD2 induces phosphorylation of Stat3 transcription factor in dental pulp cells. We conclude that intracanal treatment with RvD2 resolves inflammation and promoting calcification around root apex and healing of periapical bone lesions. The data suggest that RvD2 induces active resolution of inflammation with pulp-like tissue regeneration after root canal infection and thus maybe suitable for treating periapical lesions.

DOI： 10.3389/fimmu.2019.00307

Scopus

PubMed

researchmap

Fungal metabolite (+)-terrein suppresses IL-6/sIL-6R-induced CSF1 secretion by inhibiting JAK1 phosphorylation in human gingival fibroblasts 査読 国際誌

Satoshi Yamamoto, Kazuhiro Omori, Hiroki Mandai, Masaaki Nakayama, Saki Nakagawa, Hiroya Kobayashi, Tadashi Kunimine, Hiroshi Yoshimura, Kyosuke Sakaida, Hidefumi Sako, Soichiro Ibaragi, Tadashi Yamamoto, Hiroshi Maeda, Seiji Suga, Shogo Takashiba

Heliyon   4 ( 11 )   e00979   2018年11月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2018 The Authors Control of bacterial infection-induced inflammatory responses is one of the effective therapeutic approaches of periodontal diseases. Natural products such as lipid mediators and metabolites from microorganisms have been used for decreasing inflammation. We previously reported that (+)-terrein inhibited activation of STAT3 and ERK1/2 in interleukin-6 (IL-6) signaling cascade, leading to prevent vascular endothelial growth factor (VEGF) secretion in human gingival fibroblasts (HGFs). However, little is still known about the role of (+)-terrein on inflammatory responses. In this study, we provided the possibility of novel action that (+)-terrein inhibits activation of Janus-activated kinase 1 (JAK1), which has a central function in IL-6 signaling cascade, and alters expression of mRNAs and proteins induced by IL-6/soluble IL-6 receptor (sIL-6R) stimulation in HGFs. First, we performed PCR array to examine IL-6/sIL-6R-induced mRNA expression, and then expression of mRNA and protein of colony stimulating factor-1 (CSF1) and VEGF were clearly determined by quantitative RT-PCR and ELISA, respectively. Treatment with (+)-terrein suppressed expression of mRNA and protein of CSF1 and VEGF by IL-6/sIL-6R stimulation. Next, to test the effect of (+)-terrein on IL-6/sIL-6R signaling cascade, we demonstrated whether (+)-terrein affects phosphorylation of JAK1 and its downstream proteins, Akt and SHP-2. Western blotting revealed that (+)-terrein inhibited IL-6/sIL-6R-induced phosphorylation of JAK1, Akt, and SHP-2. Therefore, (+)-terrein suppresses IL-6/sIL-6R-induced expression of CSF1 and VEGF via inhibition of JAK1, Akt, and SHP-2. Based on our results, we suggest that (+)-terrein is a candidate compound for anti-inflammatory effect associated with IL-6 signaling.

DOI： 10.1016/j.heliyon.2018.e00979

Scopus

PubMed

researchmap

HMGB1-induced inflammatory response promotes bone healing in murine tooth extraction socket 査読

Hiroaki Aoyagi, Keisuke Yamashiro, Chiaki Hirata-Yoshihara, Hidetaka Ideguchi, Mutsuyo Yamasaki, Mari Kawamura, Tadashi Yamamoto, Shinsuke Kochi, Hidenori Wake, Masahiro Nishibori, Shogo Takashiba

Journal of Cellular Biochemistry   119 ( 7 )   5481 - 5490   2018年7月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley-Liss Inc.  

© 2018 Wiley Periodicals, Inc. High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein that is secreted into the extracellular milieu in response to inflammatory stimuli. The secreted HMGB1 has been suggested to mediate various inflammatory diseases. However, it is still unknown whether HMGB1 is involved in a healing process in the tooth extraction socket, the tissue containing gingival epithelium, and alveolar bone that is exposed to oral bacteria. In this study, we constructed a murine tooth extraction model with anti-HMGB1 neutralization antibody administration and observed the inflammatory response and bone healing process in tooth extraction sockets by molecular imaging of myeloperoxidase (MPO) activity, histological analysis, and quantitative RT-PCR. The translocation of HMGB1 from the nucleus to the cytoplasm in gingival epithelial cells and inflammatory cells was inhibited by anti-HMGB1 antibody administration. The MPO activity around the tooth extraction socket was significantly reduced, and the numbers of CD31- and CD68-positive cells were significantly lower in the anti-HMGB1 antibody treatment samples than in the control samples. The TRAP-positive cells, osteocalcin positive cells, and the neoplastic bone area were significantly lower in anti-HMGB1 antibody treatment samples than in control samples. The expression levels of IL-1β and VEGF-A were also decreased in anti-HMGB1 antibody treatment samples compared to that in control samples. Secreted HMGB1 induced initial acute inflammation and inflammatory cells recruitment after tooth extraction. HMGB1 was associated with angiogenesis and bone remodeling by osteoclast and osteoblast activation and promoted bone healing in the tooth extraction socket.

DOI： 10.1002/jcb.26710

Scopus

PubMed

researchmap

PET(18F-FDG)/CT検査を用いた慢性歯周炎患者における歯周組織炎症の評価 査読

井手口 英隆, 山城 圭介, 下江 正幸, 山本 直史, 長島 義之, 高柴 正悟

日本歯周病学会会誌   60 ( 2 )   105 - 116   2018年6月

　詳細を見る

記述言語：日本語   出版者・発行元：(NPO)日本歯周病学会  

歯周炎に対する検査方法は多数報告されているが、歯周組織炎症の程度を客観的に評価することが出来る方法は未だに確立されていない。我々は、医科領域で広く用いられているPET(18F-FDG)/CTが炎症組織の局在と炎症強度を可視化することができることに着目した。そして、乳がんの既往を有する慢性歯周炎患者に対する歯周治療の効果を、既存の歯周組織検査方法とPET(18F-FDG)/CTとで経時的に比較検討した。歯周治療が進むに従って歯周組織炎症は消失し、BOPの割合は56%から3%に、PISAは1143mm2から27mm2に改善した。さらに、歯周治療前にPET(18F-FDG)/CTで検出された18F-FDGの顕著な集積は歯周治療後には消失した。これらの結果から、PET(18F-FDG)/CTは炎症性口腔疾患に対する新規検査方法として有用と考えられる。すなわち本症例報告は、PET(18F-FDG)/CTが医科-歯科共通の検査項目となることによって、周術期の医科-歯科連携の強化や、全身疾患を有する多くの歯周炎患者に対してさらに効果的な歯周治療を行うことが出来る可能性を提案するものである。(著者抄録)

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01095&link_issn=&doc_id=20180706390006&doc_link_id=%2Fcp9perlo%2F2018%2F006002%2F006%2F0105-0116%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcp9perlo%2F2018%2F006002%2F006%2F0105-0116%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Anti-HMGB1 neutralizing antibody attenuates periodontal inflammation and bone resorption in a murine periodontitis model 査読

Chiaki Yoshihara-Hirata, Keisuke Yamashiro, Tadashi Yamamoto, Hiroaki Aoyagi, Hidetaka Ideguchi, Mari Kawamura, Risa Suzuki, Mitsuaki Ono, Hidenori Wake, Masahiro Nishibori, Shogo Takashiba

Infection and Immunity   86 ( 5 )   2018年5月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society for Microbiology  

© 2018 American Society for Microbiology. High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein that is secreted into the extracellular milieu in response to inflammatory stimuli. The secreted HMGB1 mediates various inflammatory diseases, including periodontitis; however, the underlying mechanisms of HMGB1-induced periodontal inflammation are not completely understood. Here, we examined whether anti-HMGB1 neutralizing antibody inhibits periodontal progression and investigated the molecular pathology of HMGB1 in vitro and in vivo. In vitro analysis indicated that HMGB1, granulocytemacrophage colony-stimulating factor (GM-CSF), and interleukin-1β (IL-1β) were secreted in response to tumor necrosis factor-α (TNF-α) stimuli in human gingival epithelial cells (HGECs) and human monocytic leukemia cells (THP-1) treated with phorbol myristate acetate. Increased levels of GM-CSF and IL-1β were observed in the conditioned media from TNF-α-stimulated HGECs and THP-1 in vitro. Simultaneous stimulation with TNF-α and anti-HMGB1 antibody significantly decreased TNF-α- induced inflammatory cytokine secretion. Experimental periodontitis was induced in mice using Porphyromonas gingivalis-soaked ligatures. The extracellular translocation was confirmed in gingival epithelia in the periodontitis model mice by immunofluorescence analysis. Systemic administration of anti-HMGB1 neutralizing antibody significantly inhibited translocation of HMGB1. The anti-HMGB1 antibody inhibited periodontal inflammation, expression of IL-1β and C-X-C motif chemokine ligand 1 (CXCL1), migration of neutrophils, and bone resorption, shown by bioluminescence imaging of myeloperoxidase activity, quantitative reverse transcription-PCR (RT-PCR), and micro-computed tomography analysis. These findings indicate that HMGB1 is secreted in response to inflammatory stimuli caused by periodontal infection, which is crucial for the initiation of periodontitis, and the anti-HMGB1 antibody attenuates the secretion of a series of inflammatory cytokines, consequently suppressing the progression of periodontitis.

DOI： 10.1128/IAI.00111-18

Scopus

PubMed

researchmap

Correction to: Expression of optineurin isolated from rat-injured dental pulp and the effects on inflammatory signals in normal rat kidney cells (Odontology, (2018), 106, 2, (135-144), 10.1007/s10266-017-0314-5) 査読

Kyoko Senoo, Keisuke Yamashiro, Tadashi Yamamoto, Fumio Myokai, Mari Kawamura, Shogo Takashiba

Odontology   106 ( 2 )   223   2018年4月

　詳細を見る

掲載種別：研究論文（学術雑誌）  

© 2017, The Society of The Nippon Dental University. In the original publication of the article, one of the author name was published incorrectly as “Keisuke Yamashairo” and correct name should be “Keisuke Yamashiro”.

DOI： 10.1007/s10266-017-0334-1

Web of Science

Scopus

PubMed

researchmap

Modulation of microenvironment for controlling the fate of periodontal ligament cells: the role of Rho/ROCK signaling and cytoskeletal dynamics 招待 査読

Tadashi Yamamoto, Yuki Ugawa, Mari Kawamura, Keisuke Yamashiro, Shinsuke Kochi, Hidetaka Ideguchi, Shogo Takashiba

Journal of Cell Communication and Signaling   12 ( 1 )   369 - 378   2018年3月

　詳細を見る

担当区分：筆頭著者   記述言語：英語   出版者・発行元：Springer Netherlands  

© 2017, The International CCN Society. Cells behave in a variety of ways when they perceive changes in their microenvironment; the behavior of cells is guided by their coordinated interactions with growth factors, niche cells, and extracellular matrix (ECM). Modulation of the microenvironment affects the cell morphology and multiple gene expressions. Rho/Rho-associated coiled-coil-containing protein kinase (ROCK) signaling is one of the key regulators of cytoskeletal dynamics and actively and/or passively determines the cell fate, such as proliferation, migration, differentiation, and apoptosis, by reciprocal communication with the microenvironment. During periodontal wound healing, it is important to recruit the residential stem cells into the defect site for regeneration and homeostasis of the periodontal tissue. Periodontal ligament (PDL) cells contain a heterogeneous fibroblast population, including mesenchymal stem cells, and contribute to the reconstruction of tooth-supporting tissues. Therefore, bio-regeneration of PDL cells has been the ultimate goal of periodontal therapy for decades. Recent stem cell researches have shed light on intrinsic ECM properties, providing paradigm shifts in cell fate determination. This review focuses on the role of ROCK activity and the effects of Y-27632, a specific inhibitor of ROCK, in the modulation of ECM-microenvironment. Further, it presents the current understanding of how Rho/ROCK signaling affects the fate determination of stem cells, especially PDL cells. In addition, we have also discussed in detail the underlying mechanisms behind the reciprocal response to the microenvironment.

DOI： 10.1007/s12079-017-0425-3

Scopus

PubMed

researchmap

感染、炎症、機能の観点から見た口腔検査指標の歯周病治療に対する有用性 パイロット研究 査読

畑中 加珠, 片山 広大, 井上 裕貴, 坂井田 京佑, 清水 由梨香, 鈴木 里紗, 高木 美奈, 山本 直史, 高柴 正悟

日本口腔検査学会雑誌   10 ( 1 )   58 - 63   2018年3月

　詳細を見る

記述言語：日本語   出版者・発行元：(一社)日本口腔検査学会  

目的:歯周病治療の効果を「感染」、「炎症」、そして「機能」の3つの観点から評価して、治療効果を示す指標を探った。方法:歯周病治療を終えて安定期治療に至った7症例において、歯周局所の歯周病原細菌数と9菌種の血清IgG抗体価、歯周ポケット深さとプロービング時の出血から算出する歯周炎症表面積(PISA)、そして咀嚼機能の簡易指標として残存歯の動揺度を測定した。これら4つの指標の変動を治療時期の一定ポイントで調べ、それらの相互関係を検討した。結果:歯周治療が進むにしたがって、PISA、歯の動揺度およびPorphyromonas gingivalis(Pg)に対する抗体価の数値は低下し、7症例の各時期における平均値をとると、経時的な有意差が認められた(P<0.05)。しかしながら、他の菌種に対する抗体価や歯周局所の細菌数には増加するものもみられた。結論:「感染」、「炎症」、「機能」の3つの観点から歯周病治療の効果を評価する指標として、抗Pg抗体価、PISA、そして歯の動揺度を用いることは有用であった。(著者抄録)

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J05670&link_issn=&doc_id=20180514360008&doc_link_id=http%3A%2F%2Fhdl.handle.net%2F10130%2F4539&url=http%3A%2F%2Fhdl.handle.net%2F10130%2F4539&type=%93%8C%8B%9E%8E%95%89%C8%91%E5%8Aw%81F%93%8C%8B%9E%8E%95%89%C8%91%E5%8Aw%8Aw%8Fp%8B%40%8A%D6%83%8A%83%7C%83W%83g%83%8A%81FIRUCAA%40TDC&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80092_3.gif

Effects of Lectins on initial attachment of cariogenic Streptococcus mutans 査読

Takashi Ito, Yasuhiro Yoshida, Yasuyoshi Shiota, Yuki Ito, Tadashi Yamamoto, Shogo Takashiba

Glycoconjugate Journal   35 ( 1 )   41 - 51   2018年2月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer New York LLC  

© 2017, Springer Science+Business Media, LLC. Oral bacteria initiate biofilm formation by attaching to tooth surfaces via an interaction of a lectin-like bacterial protein with carbohydrate chains on the pellicle. This study aimed to find naturally derived lectins that inhibit the initial attachment of a cariogenic bacterial species, Streptococcus mutans (S. mutans), to carbohydrate chains in saliva in vitro. Seventy kinds of lectins were screened for candidate motifs that inhibit the attachment of S. mutans ATCC 25175 to a saliva-coated culture plate. The inhibitory effect of the lectins on attachment of the S. mutans to the plates was quantified by crystal violet staining, and the biofilm was observed under a scanning electron microscope (SEM). Surface plasmon resonance (SPR) analysis was performed to examine the binding of S. mutans to carbohydrate chains and the binding of candidate lectins to carbohydrate chains, respectively. Moreover, binding assay between the biotinylated-lectins and the saliva components was conducted to measure the lectin binding. Lectins recognizing a salivary carbohydrate chain, Galβ1-3GalNAc, inhibited the binding of S. mutans to the plate. In particular, Agaricus bisporus agglutinin (ABA) markedly inhibited the binding. This inhibition was confirmed by SEM observation. SPR analysis indicated that S. mutans strongly binds to Galβ1-3GalNAc, and ABA binds to Galβ1-3GalNAc. Finally, the biotinylated Galβ1-3GalNAc-binding lectins including ABA demonstrated marked binding to the saliva components. These results suggest that ABA lectin inhibited the attachment of S. mutans to Galβ1-3GalNAc in saliva and ABA can be useful as a potent inhibitor for initial attachment of oral bacteria and biofilm formation.

DOI： 10.1007/s10719-017-9795-2

Scopus

PubMed

researchmap

IS1598 (IsPg4) distributed to abscess-forming strains of Porphyromonas gingivalis may enhance virulence through upregulation of nrdD-like gene expression 査読

Norihiro Sonoi, Hiroshi Maeda, Toshimitsu Murauchi, Tadashi Yamamoto, Kazuhiro Omori, Susumu Kokeguchi, Koji Naruishi, Shogo Takashiba

New Microbiologica   41 ( 1 )   52 - 60   2018年1月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Luigi Ponzio e figlio Editori  

©2018 by EDIMES-Edizioni Internazionali Srl. All rights reserved. An insertion sequence, IS1598 (IsPg4) has been found in virulent strains of Porphyromonas gingivalis in a murine abscess model. The present study was performed to investigate the effects of genetic rearrangements by IS1598 on the phenotypic characteristics of the virulent strains. For this purpose, we searched for a common insertion site of IS1598 among the virulent strains. Through cloning and database search, a common insertion site was identified beside an nrdD-like gene in the virulent FDC 381, W83 and W50 strains. In this region, predicted promoters of the nrdD-like gene and IS1598 are located in tandem, and accumulation of nrdD-like gene mRNA was 5-fold higher in virulent strains (W83, W50, FDC 381) than avirulent strains (ATCC33277, SU63, SUNY1021, ESO59 without IS1598). The role of the nrdD-like gene in virulence of P. gingivalis was investigated by constructing a nrdD-deficient mutant. In the murine abscess model, the parental W83 strain produced necrotic abscesses, while the nrdD-deficient mutant had almost lost this ability. Insertion of IS1598 into the nrdD-like gene promoter region may be related to the phenotypic differences in virulence among P. gingivalis strains through upregulation of the expression of this gene.

Scopus

PubMed

researchmap

Expression of optineurin isolated from rat-injured dental pulp and the effects on inflammatory signals in normal rat kidney cells

Tadashi Yamamoto

Odontology   106 ( 2 )   2018年

　詳細を見る

掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/S10266-017-0314-5

Web of Science

Scopus

researchmap

Aggregatibacter actinomycetemcomitans regulates the expression of integrins and reduces cell adhesion via integrin α5 in human gingival epithelial cells. 査読

Kochi S, Yamashiro K, Hongo S, Yamamoto T, Ugawa Y, Shimoe M, Kawamura M, Hirata-Yoshihara C, Ideguchi H, Maeda H, Takashiba S

Molecular and cellular biochemistry   436 ( 1-2 )   39 - 48   2017年12月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11010-017-3076-z

Web of Science

PubMed

researchmap

Assessment of pathogenesis of infective endocarditis by plasma IgG antibody titer test against periodontal bacteria. 査読 国際誌

Isoshima D, Yamashiro K, Matsunaga K, Shinobe M, Nakanishi N, Nakanishi I, Omori K, Yamamoto T, Takashiba S

Clinical case reports   5 ( 10 )   1580 - 1586   2017年10月

　詳細を見る

記述言語：英語  

DOI： 10.1002/ccr3.1066

PubMed

researchmap

Rho-kinase regulates extracellular matrix-mediated osteogenic differentiation of periodontal ligament cells 査読

Yuki Ugawa, Tadashi Yamamoto, Mari Kawamura, Keisuke Yamashiro, Masayuki Shimoe, Kazuya Tomikawa, Shoichi Hongo, Hiroshi Maeda, Shogo Takashiba

CELL BIOLOGY INTERNATIONAL   41 ( 6 )   651 - 658   2017年6月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

The periodontal ligament (PDL) cells contain heterogeneous mesenchymal cell populations, which have the ability to differentiate into cells that produce adjacent mineralized tissues and abundant extracellular matrix (ECM). ECM is essential not only for the homeostasis of the periodontal tissue, but also for controlling the differentiation of the PDL cells. The process of differentiation involves mechanotransduction, which links the ECM to the cytoskeleton. The present study investigated the roles of Rho-associated coiled-coil containing protein kinase (ROCK) signaling, a crucial regulator of the cytoskeleton, during ECM-mediated osteogenic differentiation of PDL cells in vitro. The PDL cells were isolated from human periodontal ligaments of extracted teeth and cultured in osteogenic medium with or without Y-27632, a pharmacological inhibitor of ROCK. ECMcoated plates were used for ECM-mediated differentiation. The osteogenic phenotype was evaluated at different time points by real-time RT-PCR for the gene encoding alkaline phosphatase (ALP) and an ALP activity assay. The effects of ROCK on cytoskeletal changes and ECM synthesis were examined by immunofluorescence analysis. Y-27632 significantly inhibited ALP at the mRNA and protein activity levels in the late stage of differentiation; concomitantly, the actin filament content and the extracellular levels of collagen-I and fibronectin were markedly decreased by Y-27632. Exogenous collagen-I and fibronectin temporally increased ALP activity, with fibronectin showing a more pronounced effect. Importantly, ECM-mediated differentiation was almost completely inhibited by Y-27632. These findings indicated that ECM-mediated differentiation is dependent on ROCK signaling, and ROCK signaling contributes to the establishment of the ECM microenvironment for PDL cell differentiation.

DOI： 10.1002/cbin.10769

Web of Science

PubMed

researchmap

Smad2 overexpression enhances adhesion of gingival epithelial cells 査読

Shoichi Hongo, Tadashi Yamamoto, Keisuke Yamashiro, Masayuki Shimoe, Kazuya Tomikawa, Yuki Ugawa, Shinsuke Kochi, Hidetaka Ideguchi, Hiroshi Maeda, Shogo Takashiba

ARCHIVES OF ORAL BIOLOGY   71   46 - 53   2016年11月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Objective: Gingival epithelial cells play an important role in preventing the initiation of periodontitis, by their hemidesmosomal adhesion to the tooth root surface. Adhesion requires integrin-extracellular matrix (ECM) interactions that are intricately regulated by transforming growth factor-beta (TGF-beta) signaling. However, the mechanisms underlying the interplay between adhesion molecules and TGF-beta, especially the respective roles of Smad2 and Smad3, remain elusive. In this study, we examined the effects of Smad overexpression on gingival epithelial cell adhesion and expression profiles of integrin and ECM-related genes.
Methods: Human gingival epithelial cells immortalized by the SV40 T-antigen were transfected with Smad2- and Smad3-overexpression vectors. A cell adhesion assay involving fluorescence detection of attached cells was performed using the ArrayScan imaging system. Real-time PCR was performed to examine the kinetics of integrin and ECM gene expression. In vitro and in vivo localization of adhesion molecules was examined by immunofluorescence analysis.
Results: By using SB431542, a specific inhibitor of the TGF-beta type I receptor, Smad2/3 signaling was confirmed to be dominant in TGF-beta 1-induced cell adhesion. The Smad2-transfectant demonstrated higher potency for cell adhesion and integrin expression (alpha 2, alpha 5, beta 4, and beta 6) than the Smad3-transfectant, whereas little or no change in ECM expression was observed in either transfectant. Moreover, the gingival epithelium of transgenic mice that overexpressed Smad2 driven by the keratin 14 promoter showed increased integrin alpha 2 expression.
Conclusion: These findings indicate the crucial role of Smad2 in increased adhesion of gingival epithelial cells via upregulation of integrin alpha 2. (C) 2016 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.archoralbio.2016.06.025

Web of Science

PubMed

researchmap

Osteogenic differentiation regulated by Rho-kinase in periodontal ligament cells 査読

Tadashi Yamamoto, Yuki Ugawa, Keisuke Yamashiro, Masayuki Shimoe, Kazuya Tomikawa, Shoichi Hongo, Shinsuke Kochi, Hidetaka Ideguchi, Hiroshi Maeda, Shogo Takashiba

DIFFERENTIATION   88 ( 2-3 )   33 - 41   2014年9月

　詳細を見る

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

The periodontal ligament is a multifunctional soft connective tissue, which functions not only as a cushion supporting the teeth against occlusal force, but is also a source of osteogenic cells that can regenerate neighboring hard tissues. Periodontal ligament cells (PDL cells) contain heterogeneous cell populations, including osteogenic cell progenitors. However, the precise mechanism underlying the differentiation process remains elusive. Cell differentiation is regulated by the local biochemical and mechanical microenvironment that can modulate gene expression and cell morphology by altering actin cytoskeletal organization mediated by Rho-associated, coiled-coil containing protein kinase (ROCK). To determine its role in PDL cell differentiation, we examined the effects of ROCK on cytoskeletal changes and kinetics of gene expression during osteogenic differentiation. PDL cells were isolated from human periodontal ligament on extracted teeth and cultured in osteogenic medium for 14 days. Y-27632 was used for ROCK inhibition assay. Osteogenic phenotype was determined by monitoring alkaline phosphatase (ALP) activity and calcium deposition by Alizarin Red staining. ROCK-induced cytoskeletal changes were examined by immunofluorescence analysis of F-actin and myosin light chain 2 (MLC2) expression. Real-time PCR was performed to examine the kinetics of osteogenic gene expression. F-actin and phospho-MLC2 were markedly induced during osteogenic differentiation, which coincided with upregulation of ALP activity and mineralization. Subsequent inhibition assay indicated that Y-27632 significantly inhibited F-actin and phospho-MLC2 expression in a dose dependent manner with concomitant partial reversal of the PDL cell osteogenic phenotype. PCR array analysis of osteogenic gene expression indicated that extracellular matrix genes, such as fibronectin 1, collagen type I and Ill, and biglycan, were significantly downregulated by Y27632. These findings indicated crucial effects of ROCK in cytoskeletal reorganization and differentiation of PDL cells toward osteogenic cells. ROCK contributes to induction of osteogenic differentiation by synergistic increases in extracellular matrix gene expression in PDL cells. (C) 2014 International Society of Differentiation, Published by Elsevier B.V. All rights reserved.

DOI： 10.1016/j.diff.2014.09.002

Web of Science

PubMed

researchmap

Overexpression of Smad2 inhibits proliferation of gingival epithelial cells 査読

M. Shimoe, T. Yamamoto, N. Shiomi, K. Tomikawa, S. Hongo, K. Yamashiro, T. Yamaguchi, H. Maeda, S. Takashiba

JOURNAL OF PERIODONTAL RESEARCH   49 ( 3 )   290 - 298   2014年6月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background and Objective
Spatiotemporal inhibition of apical migration and proliferation of gingival epithelium are significant factors involved in periodontal regeneration. Transforming growth factor beta (TGF-beta) is important in multiple aspects of wound healing, and Smad2, a downstream transcription factor of TGF-beta, has an inhibitory effect on re-epithelialization during gingival wound healing. Therefore, we investigated the effects on migration and proliferation status, and intra/extracellular signaling regulated by Smad2 overexpression in gingival epithelial cells.
Material and Methods
Gingival epithelial cells were isolated from the palatal gingival tissue of transgenic mice overexpressing Smad2 driven by the Keratin14 promoter. Smad2 expression was identified by western blotting and immunofluorescence analysis. Scratch assay and 5-bromo-2 '-deoxyuridine staining were performed to assess cell migration and proliferation. To inactivate TGF-beta type I receptor, the cultures were supplemented with SB431542. Secreted TGF-beta was quantified by ELISA. Smad2 target gene expression was examined by real-time RT-PCR and in vivo immunofluorescence analysis of gingival junctional epithelium.
Results
Smad2-overexpressing cells were confirmed to have significant phosphorylated Smad2 in the nucleus. Scratch assay and 5-bromo-2 '-deoxyuridine staining indicated that Smad2-overexpressing cells showed no significant differences in migration, but had reduced proliferation rates compared to wild-type controls. SB431542 significantly inhibited Smad2 phosphorylation, which coincided with restoration of the proliferation rate in Smad2-overexpressing cells. ELISA of TGF-beta release did not show any differences between genotypes. The cell cycle inhibitors, p15 and p21, showed significant upregulation in Smad2-overexpressing cells compared to wild-type controls. Moreover, junctional epithelium of the transgenic mice showed increased expression of P-Smad2, p15 and p21.
Conclusion
The signaling activation triggered by overexpression of Smad2 was dependent on TGF-beta type I receptor, and the activated Smad2 increased p15 and p21 expression, responsible for inhibiting cell cycle entry, resulting in antiproliferative effects on gingival epithelial cells. Understanding of Smad2-induced signaling would be useful for possible clinical application to regulate gingival epithelial downgrowth.

DOI： 10.1111/jre.12106

Web of Science

researchmap

細菌感染度を評価しながら包括的歯周治療を行った広汎型侵襲性歯周炎患者の一症例 査読

冨川 和哉, 河野 隆幸, 山本 直史, 岩本 義博, 下江 正幸, 山口 知子, 本郷 昌一, 宮本 学, 前田 博史, 高柴 正悟

日本歯周病学会会誌   55 ( 4 )   340 - 348   2013年12月

　詳細を見る

記述言語：日本語   出版者・発行元：(NPO)日本歯周病学会  

歯周病に対する感受性が高い侵襲性歯周炎患者の治療においては、徹底した感染のコントロールによる疾患活動性の抑制が必要である。とりわけ、歯列不正を伴う歯周炎患者に矯正治療を行うことは、長期に渡る感染のコントロールを行う上で非常に有効である。しかし、歯周炎患者に矯正治療を行う場合に、感染がコントロールされている歯周状態かどうかを決定する基準は未だ明確でない。今回報告するのは、Agregatibacter actinomycetemcomitans(Aa)の感染が主な病態形成因子と考えられる、初診時22歳の広汎型侵襲性歯周炎患者に対して、矯正治療を含めた包括的歯周治療を行った症例である。初診以降、臨床計測値の変化に加えて、細菌DNA検査と歯周病原細菌に対する血清IgG抗体価検査を用いて、歯周病原細菌の感染度を評価した。その結果、歯周外科治療を含む感染源除去によって、細菌DNA検査でAaが検出されず、Aaに対する血清IgG抗体価が健常者レベルに推移したことを矯正治療移行前に確認した。すなわち、歯周病原細菌感染度が低下したと判断した後に、矯正治療を行うことで、現在まで良好なSPTを維持している。本症例においては、Aaの感染度の低下を細菌DNA検査と血清IgG抗体価を用いて評価することによって、客観的な根拠をもって矯正治療に移行できたと考える。(著者抄録)

DOI： 10.2329/perio.55.340

researchmap

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J01095&link_issn=&doc_id=20140117230007&doc_link_id=%2Fcp9perlo%2F2013%2F005504%2F008%2F0340-0348%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcp9perlo%2F2013%2F005504%2F008%2F0340-0348%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Serum antibody response to group II chaperonin from Methanobrevibacter oralis and human chaperonin CCT 査読

Kimito Hirai, Hiroshi Maeda, Kazuhiro Omori, Tadashi Yamamoto, Susumu Kokeguchi, Shogo Takashiba

PATHOGENS AND DISEASE   68 ( 1 )   12 - 19   2013年6月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Both group I (HSP60) and group II (CCT) chaperonins are targets of autoantibodies. Autoimmune reactions to HSP60 have been well characterized, while immune reactions to group II chaperonin have not been clarified. Methanobrevibacter oralis is a suspected periodontal pathogen with group II chaperonin. In this study, serum responses to M.oralis chaperonin, human HSP60, and CCT subunits were examined using sera from patients with periodontitis and autoimmune diseases. In comparison with healthy controls, periodontitis patients showed significantly higher responses to CCT4 and CCT8 on dot blot analysis. Signals for CCT3 and CCT8 in autoimmune disease patients were significantly higher than in controls. Significant differences were also demonstrated by Western blotting in anti-CCT4 response in both patient groups. All subjects showed strong reactivity to M.oralis chaperonin and faint signals to human HSP60. Autoantibodies were raised against CCT rather than HSP60; and CCT3, CCT4, and CCT8 were shown to be the main targets. Host immune systems may be frequently exposed to chaperonins of Archaea in various habitats. Although further studies of the cross-reactivity between M.oralis chaperonin and human CCT are required, anti-CCT autoantibodies may be involved in the pathogenesis of periodontitis and autoimmune diseases.

DOI： 10.1111/2049-632X.12041

Web of Science

PubMed

researchmap

Medical microbiological approach to Archaea in oral infectious diseases 査読

Hiroshi Maeda, Kimito Hirai, Junji Mineshiba, Tadashi Yamamoto, Susumu Kokeguchi, Shogo Takashiba

Japanese Dental Science Review   49 ( 2 )   72 - 78   2013年5月

　詳細を見る

記述言語：英語  

Recent advances in molecular biological techniques have yielded large amounts of information regarding the oral microflora. The microbiological communities were shown to be more diverse than previously thought and to include a number of previously uncharacterized microorganisms. The range of research targets of microorganisms associated with oral diseases has been expanded to include these unknown or uncharacterized organisms. These organisms include the Archaea. A series of recent reports suggested these microorganisms to be potential pathogens involved in periodontitis and apical periodontitis mainly based on the detection frequency or their increased numbers in diseased sites in association with the severity or symptoms of disease. However, it cannot be concluded that Archaea are oral pathogens based on such circumstantial evidence. Further studies are required to investigate the potential pathogenic mechanisms of action of these organisms. This will require investigation of the antigenic properties of the Archaea and synergism with other established oral pathogens. Especially, studies of the host immune response will provide insight into the medical impact of Archaea as suspected pathogens. © 2013 Japanese Association for Dental Science.

DOI： 10.1016/j.jdsr.2013.01.002

Scopus

researchmap

Smad2 Decelerates Re-epithelialization during Gingival Wound Healing 査読

K. Tomikawa, T. Yamamoto, N. Shiomi, M. Shimoe, S. Hongo, K. Yamashiro, T. Yamaguchi, H. Maeda, S. Takashiba

JOURNAL OF DENTAL RESEARCH   91 ( 8 )   764 - 770   2012年8月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS INC  

During periodontal regeneration, inhibition of gingival downgrowth is necessary to promote migration of mesenchymal cells into the defects. Transforming growth factor (TGF)-beta is a pleiotropic cytokine that has numerous cell functions, including regulation of epithelial growth. Recent studies have shown that Smad2, a downstream transcription factor of TGF-beta, plays crucial roles in wound healing in the epithelia. Therefore, we investigated the effects of Smad2 overexpression on re-epithelialization of gingival wounds. Transgenic mice overexpressing smad2 driven by the keratin 14 promoter (k14-smad2) were confirmed to have significant Smad2 phosphorylation in gingival basal epithelia. Punch wounds were made in the palatal gingiva, and wound healing was assessed histologically for 7 days. Re-epithelialization was significantly retarded on day 2, while collagen deposition was enhanced on day 7 in k14-smad2 compared with wild-type mice. Moreover, expression of keratin 16 (K16), an indicator of keratinocyte migration, was significantly inhibited in wound-edge keratinocytes in k14-smad2. The inhibition of K16 coincided with the induction of Smad2 in the corresponding epithelia, while BrdU incorporation was unaffected. These results indicated that Smad2 has inhibitory effects in regulating keratinocyte migration during gingival wound healing. TGF-beta/Smad2 signaling mediating alteration of K16 expression must be tightly regulated during periodontal regeneration.

DOI： 10.1177/0022034512451449

Web of Science

researchmap

The promotional effect of IL-22 on mineralization activity of periodontal ligament cells 査読

Nahoko Kato-Kogoe, Toshihiro Nishioka, Mutsuki Kawabe, Fusa Kataoka, Koji Yamanegi, Naoko Yamada, Masaki Hata, Tadashi Yamamoto, Keiji Nakasho, Masahiro Urade, Nobuyuki Terada, Hideki Ohyama

CYTOKINE   59 ( 1 )   41 - 48   2012年7月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

Objectives: Interleukin (IL)-22 acts on non-immune cells to induce anti-microbial responses, protection from tissue damage, and enhance cell regeneration. However, little is known about the involvement of IL-22 in periodontal biology. This study investigated the biological effects of IL-22 on periodontal ligament (PDL) cells as part of studies to assess the involvement of IL-22 in periodontal disease.
Materials and methods: Gene expression levels of IL-22 and its receptors in PDL cells and gingival tissue samples were evaluated by real-time PCR. Proliferative responses and mineralized-matrix forming activities of PDL cells were examined in the presence and absence of IL-22.
Results: In contrast to the expression of IL-22 receptors detected in PDL tissues and their cell lines, gingival tissues showed modest or no gene expressions of IL-22. The production of several cytokines including IL-11, IL-8 and CCL2 was upregulated by IL-22 treatment of PDL cells in a dose-dependent manner. IL-22 treatment had no effect on the proliferative response in PDL cells. Meanwhile, IL-22 precipitated mineralized nodule formation and induced gene expressions of RUNX2,MSX2 and osteocalcin in PDL cells, suggesting that IL-22 enhances the mineralized matrix-forming activities of PDL cells.
Conclusion: IL-22 has the potential to promote mineralizing activity in PDL cells and to develop appropriate regenerative therapy. (C) 2012 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.cyto.2012.03.024

Web of Science

PubMed

researchmap

血清抗体価検査を応用して治療した広汎型侵襲性歯周炎患者の15年間の経過 査読

冨川 和哉, 岩本 義博, 大江 丙午, 新井 英雄, 山本 直史, 前田 博史, 高柴 正悟

日本歯周病学会会誌   54 ( 2 )   193 - 202   2012年6月

　詳細を見る

記述言語：日本語   出版者・発行元：(NPO)日本歯周病学会  

歯周病に対する感受性が高い侵襲性歯周炎患者の治療においては，徹底した感染コントロールを行い，疾患活動性を抑制する事が要求される。近年，歯周病原細菌の感染量や歯周炎の活動性を評価するために，PCR 法を応用した細菌 DNA 検査や血清抗体価検査が活用されるようになってきた。今回報告するのは，好中球貪食能が低下傾向であった広汎型侵襲性歯周炎患者の症例である。患者は 25 歳の女性であり，歯周 基本治療，歯周組織再生療法を含む歯周外科治療，そして最終補綴治療を経て SPT に移行し，初診から 15 年間にわたって，臨床計測値の変化および歯周病原細菌に対する血清 IgG 抗体価の変動をモニタリングしている。これによって，SPT 期間中に歯周組織の破壊が進行した 26 の臨床所見と血清 IgG 抗体価の変動を捉えることができた。26 以外の歯周組織は SPT 期間を通して安定した状態を示していたが，血清 IgG 抗体価は 26 の組織破壊の進行と連動して高値を示した。本症例においては局所的な歯周炎の活動性が血清 IgG 抗体価検査によって評価できたと考える。日本歯周病学会会誌（日歯病誌）54(2)：193-202, 2012

DOI： 10.2329/perio.54.193

CiNii Article

researchmap

Chronic periodontitis with multiple risk factor syndrome: a case report. 査読 国際誌

Masayuki Shimoe, Tadashi Yamamoto, Yoshihiro Iwamoto, Nobuyuki Shiomi, Hiroshi Maeda, Fusanori Nishimura, Shogo Takashiba

Journal of the International Academy of Periodontology   13 ( 2 )   40 - 7   2011年7月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Multiple risk factor syndrome is a clustering of cardiovascular risk factors, such as diabetes, dyslipidemia, hypertension, and obesity associated epidemiologically with insulin resistance. This report describes the clinical course of a patient suffering from severe periodontitis with multiple risk factor syndrome, and discusses the association between periodontal infection and systemic health. METHODS: The patient had a history of type 2 diabetes, dyslipidemia, and hypertension for over 10 years. At baseline, her hemoglobin A1 c was 8.1%. However, she had no diabetic complications except periodontitis. The IgG antibody titers against Porphyromonas gingivalis FDC 381 and SU63 were elevated above the mean of healthy subjects +2 standard deviations. Intensive periodontal treatment, including periodontal surgery, was performed to reduce periodontal infection and bacteremia. Her systemic and periodontal conditions were evaluated longitudinally for 10 years. RESULTS: Following periodontal treatment, antibody titers against Porphyromonas gingivalis and hemoglobin A1c values were significantly improved. The other clinical data and medication for her systemic condition also remained stable during supportive periodontal therapy. However, she developed myocardial infarction, and showed continuous deterioration of hemoglobin A1 c level and periodontitis. CONCLUSION: The long-term clustering of risk factors, such as diabetes, dyslipidemia, hypertension, and periodontitis, are associated with the development of myocardial infarction. Treatment of systemic conditions in combination with comprehensive periodontal treatment is important in management of patients with multiple risk factor syndrome.

PubMed

researchmap

Rapid detection of mecA and spa by the loop-mediated isothermal amplification (LAMP) method. 査読 国際誌

Y Koide, H Maeda, K Yamabe, K Naruishi, T Yamamoto, S Kokeguchi, S Takashiba

Letters in applied microbiology   50 ( 4 )   386 - 92   2010年4月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: To develop a detection assay for staphylococcal mecA and spa by using loop-mediated isothermal amplification (LAMP) method. METHODS AND RESULTS: Staphylococcus aureus and other related species were subjected to the detection of mecA and spa by both PCR and LAMP methods. The LAMP successfully amplified the genes under isothermal conditions at 64 degrees C within 60 min, and demonstrated identical results with the conventional PCR methods. The detection limits of the LAMP for mecA and spa, by gel electrophoresis, were 10(2) and 10 cells per tube, respectively. The naked-eye inspections were possible with 10(3) and 10 cells for detection of mecA and spa, respectively. The LAMP method was then applied to sputum and dental plaque samples. The LAMP and PCR demonstrated identical results for the plaque samples, although frequency in detection of mecA and spa by the LAMP was relatively lower for the sputum samples when compared to the PCR methods. CONCLUSION: Application of the LAMP enabled a rapid detection assay for mecA and spa. The assay may be applicable to clinical plaque samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The LAMP offers an alternative detection assay for mecA and spa with a great advantage of the rapidity.

DOI： 10.1111/j.1472-765X.2010.02806.x

PubMed

researchmap

Highly expressed genes in a rough-colony-forming phenotype of Aggregatibacter actinomycetemcomitans: implication of a mip-like gene for the invasion of host tissue 査読

Takemasa Maeda, Hiroshi Maeda, Kokoro Yamabe, Junji Mineshiba, Ichiro Tanimoto, Tadashi Yamamoto, Koji Naruishi, Susumu Kokeguchi, Shogo Takashiba

FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY   58 ( 2 )   226 - 236   2010年3月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aggregatibacter actinomycetemcomitans, a potent pathogen of periodontitis, typically grows as a rough and adherent colony on primary isolated cultures. The colony transforms into a smooth phenotype during repeated subculture. In this study, we aimed to identify highly expressed genes in the rough-colony-forming phenotype for isolation of host-induced genes. Using a cDNA-subtractive hybridization technique, three genes, homologous to a macrophage infectivity potentiator gene (mip), peroxiredoxin gene (prx) and outer membrane protein gene (ompA), were identified. The expression levels of these genes in the rough-colony-forming phenotype were 4-10-fold higher as compared with the smooth-colony-forming phenotype. Attention was focused on the mip-like gene, and a recombinant protein and a deficient mutant were constructed. The recombinant protein reacted with sera from patients with periodontitis, suggesting the production of the Mip-like protein in periodontal lesions. Viable quantitative invasion assay demonstrated that the viable cell counts of the wild-type strain that invaded HeLa cells were more than fourfold as compared with the mip-deficient mutant. The expression of the mip-like gene, prx-like gene and ompA-like gene may be enhanced in the host, and the mip-like gene may play an important role in the infection of A. actinomycetemcomitans, especially in its invasion of the epithelium.

DOI： 10.1111/j.1574-695X.2009.00624.x

Web of Science

PubMed

researchmap

Oligonucleotide array analysis of cyclic tension-responsive genes in human periodontal ligament fibroblasts 査読

Keisuke Yamashiro, Fumio Myokai, Koichi Hiratsuka, Tadashi Yamamoto, Kyoko Senoo, Hideo Arai, Fusanori Nishimura, Yoshimitsu Abiko, Shogo Takashiba

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY   39 ( 5 )   910 - 921   2007年

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Mechanical stress results in differential gene expression that is critical to convert the stimulus into biochemical signals. Under physiological stress such as occlusal force, human periodontal ligament fibroblasts (HPLF) are associated with homeostasis of periodontal tissues however the changes in response to mechanotransduction remain uncharacterized. We hypothesized that cyclic tension-responsive (CT) genes may be used to identify a set of fundamental pathways of mechanotransduction. Our goal was to catalogue CT genes in cultured HPLE HPLF were subjected to cyclic tension up to 16 h, and total RNA was isolated from both tension-loaded and static HPLE The oligonucleotide arrays analysis revealed significant changes of mRNA accumulation for 122 CT genes, and their kinetics were assigned by the K-means clustering methods. Ingenuity Pathway Analysis was completed for HPLF mechanotransduction using 50 CT genes. This analysis revealed that cyclic tension immediately down-regulated all nuclear transcription factors except v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) reacting as an early responsive gene. In turn, transcription factors such as tumor protein p53 binding protein 2 (TP53BP2), and extra-nuclear molecules such as adrenergic receptor beta 2 (ADRB2) were up-regulated after 1-2 h, which may result in fundamental HPLF functions to adapt to cyclic tension. Subsequent inhibition assays using Y27632, a pharmacologic inhibitor of Rho-associated kinase (ROCK), suggested that HPLF has both ROCK-dependent and ROCK-independent CT genes. Mechanical stress was found to effect the expression of numerous genes, in particular, expression of an early responsive gene; FOS initiates alteration of HPLF behaviors to control homeostasis of the periodontal ligament. (C) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.biocel.2007.01.015

Web of Science

PubMed

researchmap

Inhibition of SMAD2 expression prevents murine palatal fusion 査読

N Shiomi, XM Cui, T Yamamoto, T Saito, CF Shuler

DEVELOPMENTAL DYNAMICS   235 ( 7 )   1785 - 1793   2006年7月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

Transforming growth factor (TGF)-beta 3 is known to regulate the disappearance of murine medial edge epithelium (MEE) during palatal fusion. Our previous studies showed that SMAD2, a TGF-beta signaling mediator, was expressed and phosphorylated primarily in the MEE and that SMAD2 phosphorylation in the MEE was temporospatially regulated by TGF-beta 3. The goal of this study was to examine the requirement for SMAD2 to complete the developmental events necessary for palatal fusion. SMAD2 expression was inhibited with Smad2 siRNA transfection into palatal tissues in vitro. The results showed that Smad2 siRNA transfection resulted in the maintenance of MEE cells in the palatal midline. Western blot and immunofluorescence analyses confirmed that the endogenous SAUD2 and phospho-SMAD2 levels were reduced following siRNA transfection. The SMAD3 level was not altered by the Smad2 siRNA transfection. The persistence of the MEE and the decreased SMAD2/phospho-SMAD2 levels were coincident with increased MEE cell proliferation. Addition of exogenous TGF-beta 3 increased p-SMAD2 level but not the total SMAD2 level. Therefore, exogenous TGF-beta 3 was not able to induce p-SMAD2 enough to rescue the palatal phenotype in the Smad2 siRNA group. The results indicated that the endogenous SMAD2 level is crucial in the regulation of disappearance of MEE during palatal fusion.

DOI： 10.1002/dvdy.20819

Web of Science

PubMed

researchmap

培養ヒト歯根膜線維芽細胞における高浸透圧刺激によるsgk発現に関する研究 査読

明貝 文夫, 妹尾 京子, 山城 圭介, 山本 直史, 小柳津 功介, 新井 英雄, 西村 英紀, 高柴 正悟

日本歯科保存学雑誌   48 ( 6 )   939 - 945   2005年12月

　詳細を見る

記述言語：日本語   出版者・発行元：(NPO)日本歯科保存学会  

浸透圧の上昇に応答して発現上昇するとされるsgk遺伝子が培養ヒト歯根膜線維芽細胞(HPLF)においてどのような発現動態を示すか調べるとともに,sgk発現におけるアクチン細胞骨格の関与について検討した.HPLFにおいても浸透圧の上昇に伴ってsgk発現は上昇することが明らかになり,この発現変化はアクチン細胞骨格に関係する刺激伝達系によって制御されていることが示唆された

CiNii Article

researchmap

Effect of N '-nitrosonornicotine (NNN) on murine palatal fusion in vitro 査読

T Saito, XM Cui, T Yamamoto, N Shiomi, P Bringas, CF Shuler

TOXICOLOGY   207 ( 3 )   475 - 485   2005年2月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI IRELAND LTD  

Maternal smoking has been linked to an increased risk for orofacial clefts. N'-nitrosonornicotine (NNN) is one of the tobacco-specific nitrosamines that has been shown to be Linked to the deleterious effects of tobacco and could be linked to the formation of cleft palate birth defects. The effect of NNN on palatal fusion was examined using an in vitro organ culture model of palatal development. The organ cultures were exposed to NNN (0.0 1, 0. 1, 1, 10 and 100 mM) and the effects on palatal development characterized at defined points. Palatal fusion was evaluated at embryonic day 13 (E 13) + 72 h by characterizing the remaining medial edge epithelium (MEE) and determining the extent of fusion compared to controls. The NNN-treated group (I MM) had more MEE remaining in the palatal midline than the untreated group at E 13 + 72 h (P &lt; 0.05). Changes in cell proliferation in the MEE resulting from NNN exposure were examined by BrdU incorporation in replicating DNA. Changes in the pattern of MEE cell death were examined by TUNEL. BrdU incorporation and TUNEL staining showed that the NNN (1 mM)-treated palates had more MEE cell proliferation and less apoptosis than the untreated-palates at E 13 + 24 h (P &lt; 0.05). The mechanism altered by NNN was further evaluated by characterizations of extracellular signal-regulated kinase (ERK) 1/2, p38 and c-jun amino-terminal kinase (INK). NNN at I mM induced ERK1/2 phosphorylation, but reduced p38 phosphorylation (P&LT;0.05, P&LT; 0.01, respectively) in the MEE. The results suggest that NNN inhibited palatal fusion by effects on cell proliferation and MEE cell death. &COPY; 2004 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.tox.2004.10.015

Web of Science

PubMed

researchmap

Overexpression of Smad2 in Tgf-beta 3-null mutant mice rescues cleft palate 査読

XM Cui, N Shiomi, JC Chen, T Saito, T Yamamoto, Y Ito, P Bringas, Y Chat, CF Shuler

DEVELOPMENTAL BIOLOGY   278 ( 1 )   193 - 202   2005年2月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Transforming growth factor (TGF)-beta3 is an important contributor to the regulation of medial edge epithelium (MEE) disappearance during palatal fusion. SMAD2 phosphorylation in the MEE has been shown to be directly regulated by TGF-beta3. No phospho-SMAD2 was identified in the MEE in Tgf-beta3-null mutant mice (Tgf-beta(-1-)), which was correlated with the persistence of the MEE and failure of palatal fusion. In the present study, the cleft palate phenotype in Tgf-beta3(-/-) mice was rescued by overexpression of a Smad2 transgene in Keratin 14-synthesizing MEE cells following mating Tgf-beta3 heterozygous mice with Keratin 14 promoter directed Smad2 transgenic mice (K14-Smad2). Success of the rescue could be attributed to the elevated phospho-SMAD2 level in the MEE, demonstrated by two indirect evidences. The rescued palatal fusion in Tgf-beta3(-/-)/K14-Smad2 mice, however, never proceeded to the junction of primary and secondary palates and the most posterior border of the soft palate, despite phospho-SMAD2 expression in these regions at the same level as in the middle portion of the secondary palate. The K14-Smad2 transgene was unable to restore all the functional outcomes of TGF-beta3. This may indicate an anterior-posterior patterning in the palatal shelves with respect to TGF-beta3 signaling and the mechanism of secondary palatal fusion. (C) 2004 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ydbio.2004.10.023

Web of Science

PubMed

researchmap

Identification of genes differentially regulated in rat alveolar bone wound healing by subtractive hybridization 査読

T Ohira, F Myokai, N Shiomi, K Yamashiro, T Yamamoto, Y Murayama, H Arai, F Nishimura, S Takashiba

JOURNAL OF DENTAL RESEARCH   83 ( 7 )   546 - 551   2004年7月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R  

Periodontal healing requires the participation of regulatory molecules, cells, and scaffold or matrix. Here, we hypothesized that a certain set of genes is expressed in alveolar bone wound healing. Reciprocal subtraction gave 400 clones from the injured alveolar bone of Wistar rats. Identification of 34 genes and analysis of their expression in injured tissue revealed several clusters of unique gene regulation patterns, including the up-regulation at 1 wk of cytochrome c oxidase regulating electron transfer and energy metabolism, presumably occurring at the site of inflammation; up-regulation at 2.5 wks of pro-alpha-2 type I collagen involving the formation of a connective tissue structure; and up-regulation at 1 and 2 wks and down-regulation at 2.5 and 4 wks of ubiquitin carboxyl-terminal hydrolase 13 involving cell cycle, DNA repair, and stress response. The differential expression of genes may be associated with the processes of inflammation, wound contraction, and formation of a connective tissue structure.

Web of Science

researchmap

Role of ERK1/2 signaling during EGF-induced inhibition of palatal fusion 査読

T Yamamoto, XM Cui, CF Shuler

DEVELOPMENTAL BIOLOGY   260 ( 2 )   512 - 521   2003年8月

　詳細を見る

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

During mammalian palatal fusion, the medial edge epithelial (MEE) cells must stop DNA synthesis prior to the initial contact of opposing palatal shelves and thereafter selectively disappear from the midline. Exogenous EGF has been shown to inhibit the cessation of DNA synthesis and induce cleft palate; however, the precise intracellular mechanism has not been determined. We hypothesized that EGF signaling acting via ERK1/2 would maintain MEE DNA synthesis and cell proliferation and consequently inhibit the process of palatal fusion. Palatal shelves from E13 mouse embryos were maintained in organ cultures and stimulated with EGF. EGF-treated palates failed to fuse with intact MEE and had significant ERK1/2 phosphorylation. Both EGF-induced ERK1/2 phosphorylation and BrdU-incorporation were localized in the nucleus of MEE cells. Subsequent inhibition assays using U0126, a specific inhibitor of ERK1/2 phosphorylation, were conducted. U0126 inhibited EGF-induced ERK1/2 phosphorylation in a dose-dependent manner and consequently MEE cells stopped proliferation. The threshold of ERK1/2 inactivation to stop MEE DNA synthesis coincides with the level required to rescue the EGF-induced cleft palate phenotype. These results indicate that EGF-induced inhibition of palatal fusion is dependent on nuclear ERK1/2 activation and that this mechanism must be tightly regulated during normal palatal fusion. (C) 2003 Elsevier Inc. All rights reserved.

DOI： 10.1016/S0012-1606(03)00275-6

Web of Science

PubMed

researchmap

Gene profiling in human periodontal ligament fibroblasts by subtractive hybridization 査読

T Yamamoto, F Myokai, F Nishimura, T Ohira, N Shiomi, K Yamashiro, H Arai, Y Murayama, S Takashiba

JOURNAL OF DENTAL RESEARCH   82 ( 8 )   641 - 645   2003年8月

　詳細を見る

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R  

Genes expressed by human periodontal ligament fibroblasts (HPFs)are likely to be associated with specific functions of the ligament. The aim of this study is to profile genes expressed highly by HPFs. A library (6 x 103 pfu)was constructed, followed by subtraction of HPF cDNAs with human gingival fibroblast (HGF) cDNAs. Reverse-dot hybridization revealed that 33 clones expressed higher levels of specific mRNAs in HPFs than in HGFs. These were mRNAs for known genes including several associated with maturation and differentiation of cells. None had been reported in PFs. One clone, PDL-29 identified as a COX assembly factor, showed much stronger mRNA expression in HPFs than in HGFs in culture. In rat periodontium, however, PDL-29 mRNA expression was similar in PFs and GFs. These results suggest that HPFs express many previously unreported genes associated with maturation and differentiation, but expression can differ in vitro and in vivo.

Web of Science

researchmap

TGF-beta3-dependent SMAD2 phosphorylation and inhibition of MEE proliferation during palatal fusion 査読

Cui XM, Chai Y, Chen J, Yamamoto T, Ito Y, Bringas P, Shuler CF

Dev Dyn   227 ( 3 )   387 - 394   2003年7月

　詳細を見る

掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/dvdy.10326

Web of Science

CiNii Article

researchmap

Unique genes induced by mechanical stress in periodontal ligament cells 査読

F Myokai, M Oyama, F Nishimura, T Ohira, T Yamamoto, H Arai, S Takashiba, Y Murayama

JOURNAL OF PERIODONTAL RESEARCH   38 ( 3 )   255 - 261   2003年6月

　詳細を見る

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL MUNKSGAARD  

Objectives: The aim of this study is to isolate mechanical stress-induced genes (MSGens) from human periodontal ligament (PDL) cells and to analyze profiles of the mRNA expression of these genes.
Background: Differential expression of genes in PDL cells under physiological stress such as occlusal force is thought to be orchestrated not only for the remodeling of PDL itself but also for the repair and regeneration of periodontal tissues. However, little is known about the genes expressed in PDL cells under mechanical stress.
Methods: The cDNA from mechanical stress-applied human PDL cells was subtracted against the cDNA from static control cells. The subtracted cDNA was amplified by polymerase chain reaction (PCR) and cloned for further analysis.
Results: Among 68 independent clones isolated, 15 contained DNA fragments greater than 250 bp. Reverse Northern analysis revealed a marked induction of MSGen-15 and MSGen-28 mRNA expression in the mechanical stress-applied cells. However, little difference in the magnitude of expression for the other MSGens was detected between the stress-applied cells and the control cells. After nucleotide sequencing and the analysis of homology with known genes, five clones were identified; ribosomal protein S27 (MSGen-9), MRG 15 (MSGen-15), androgen-binding protein (MSGen-18), cathepsin H (MSGen-28), and cytochrome c (MSGen-47). Interestingly, it has been reported that MRG 15 is a novel transcription factor involved in the regulation of cell growth and senescence. The remaining 10 clones, classified into six sequence types, had no significant homology with any known genes.
Conclusions: These results suggest that many known and unknown genes are expressed in response to mechanical stress in PDL cells, and that a transcription factor, MRG 15, may be responsible for molecular events in PDL cells under mechanical stress.

DOI： 10.1034/j.1600-0765.2003.00602.x

Web of Science

PubMed

researchmap