Faculty Profiles - TAKASHIBA Shogo

Papers - TAKASHIBA Shogo

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

Senoo K, Yamashiro K, Yamamoto T, Myokai F, Kawamura M, Takashiba S

Odontology 106 ( 2 ) 135 - 144 2018.4

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

We previously isolated rat 14.7K-interacting protein-2 (rFIP-2) from the rat-wounded pulp. The protein, homologous to human FIP-2, is known as optineurin and was initially identified as a novel tumor necrosis factor-α (TNF-α)-inducible protein, and more recently, as an autophagy receptor. However, the biological role of optineurin in dental pulp remains elusive. We hypothesized that optineurin has a crucial role in regulating molecular processes during pulp inflammatory responses induced by TNF-α. We examined the kinetics of optineurin expression in pulp inflammation. Optineurin localization and expression were examined using rat pulp fibroblasts. The cells were treated with pharmacological inhibitors for TNF-α-induced inflammatory signals or with hydrogen peroxide as apoptotic stimuli. Stable optineurin-knockdown cells (OPTN-KD cells) were established by transfecting normal rat kidney cells with a vector expressing optineurin-specific small interfering RNA. Cell proliferation and the profiles of cytokines and intracellular signaling molecules were examined using OPTN-KD cells stimulated by TNF-α. Optineurin was localized in the cytoplasm and then translocated into the nucleus upon apoptotic stimuli. Optineurin expression was increased by TNF-α and decreased by a specific inhibitor of c-Jun N-terminal kinase. The OPTN-KD cells secreted smaller amounts of monocyte chemotactic protein-1 (MCP-1) and intracellular MCP-1 mRNA, and cell proliferation was significantly increased. Apoptosis-related signaling molecules were downregulated in OPTN-KD cells. These results demonstrated that optineurin is a crucial molecule mediated by TNF-α, which induces the production of inflammatory factors and apoptosis signaling, suggesting the presence of signaling interactions between optineurin and a transcription factor for MCP-1.

DOI： 10.1007/s10266-017-0314-5

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Modulation of microenvironment for controlling the fate of periodontal ligament cells: the role of Rho/ROCK signaling and cytoskeletal dynamics Reviewed International journal

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

Journal of Cell Communication and Signaling 12 ( 1 ) 369 - 378 2018.3

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Netherlands

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

The KCNQ1 gene polymorphism as a shared genetic risk for rheumatoid arthritis and chronic periodontitis in Japanese adults: A pilot case-control study. Reviewed International journal

Kobayashi T, Kido JI, Ishihara Y, Omori K, Ito S, Matsuura T, Bando T, Wada J, Murasawa A, Nakazono K, Mitani A, Takashiba S, Nagata T, Yoshie H

Journal of periodontology 89 ( 3 ) 315 - 324 2018.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: A number of studies have suggested a bidirectional relationship of periodontitis with rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM). However, the genetic factors that underlie these relationships have not been elucidated. METHODS: We conducted a multicenter case-control study that included 185 patients with RA and chronic periodontitis (CP), 149 patients with T2DM and CP, 251 patients with CP, and 130 systemically and periodontally healthy controls from a cohort of Japanese adults to assess the shared genetic risk factors for RA and CP as well as for T2DM and CP. A total of 17 candidate single nucleotide polymorphisms (SNPs) associated with RA, T2DM, and CP were genotyped. RESULTS: Multiple logistic regression analyses revealed that the KCNQ1 rs2237892 was significantly associated with comorbidity of RA and CP (P = 0.005) after adjustment for age, sex, and smoking status. The carriers of the T allele among patients with RA and CP showed significantly higher disease activity scores including 28 joints using C-reactive protein values than the non-carriers (P = 0.02), although the age, female percentage, and smoking status were comparable. Other SNPs were not associated with comorbidity of RA and CP, T2DM and CP, or susceptibility to CP. CONCLUSION: The results of the present pilot study suggest for the first time that the KCNQ1 rs2237892 may constitute a shared genetic risk factor for RA and CP, but not for T2DM and CP in Japanese adults.

DOI： 10.1002/JPER.17-0412

Web of Science

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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 Reviewed

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 2018.3

Authorship：Last author,　Corresponding author Language：Japanese Publisher：(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)

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

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

New Microbiologica 41 ( 1 ) 52 - 60 2018.1

Authorship：Last author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Luigi Ponzio e figlio Editori

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.

Regulatory mechanism of CCN2 production by serotonin (5-HT) via 5-HT2A and 5-HT2B receptors in chondrocytes Reviewed

Ayaka Hori, Takashi Nishida, Shogo Takashiba, Satoshi Kubota, Masaharu Takigawa

PLOS ONE 12 ( 11 ) e0188014 - e0188014 2017.11

Keisuke Yamashiro, Aki Sato, Fumihiko Okazaki, Makoto Nakano, Koichi Sawaki, Yasuhisa Hirata, Eiki Yamachika, Seiji Iida, Shogo Takashiba

Clinical Case Reports 5 ( 2 ) 97 - 103 2017.2

Assessing the progression of chronic periodontitis using subgingival pathogen levels: a 24-month prospective multicenter cohort study. Reviewed International journal

E Kakuta, Y Nomura, T Morozumi, T Nakagawa, T Nakamura, K Noguchi, A Yoshimura, Y Hara, O Fujise, F Nishimura, T Kono, M Umeda, M Fukuda, T Noguchi, N Yoshinari, C Fukaya, S Sekino, Y Numabe, N Sugano, K Ito, H Kobayashi, Y Izumi, H Takai, Y Ogata, S Takano, M Minabe, A Makino-Oi, A Saito, Y Abe, S Sato, F Suzuki, K Takahashi, T Sugaya, M Kawanami, N Hanada, S Takashiba, H Yoshie

BMC oral health 17 ( 1 ) 46 - 46 2017.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The diagnosis of the progression of periodontitis presently depends on the use of clinical symptoms (such as attachment loss) and radiographic imaging. The aim of the multicenter study described here was to evaluate the diagnostic use of the bacterial content of subgingival plaque recovered from the deepest pockets in assessing disease progression in chronic periodontitis patients. METHODS: This study consisted of a 24-month investigation of a total of 163 patients with chronic periodontitis who received trimonthly follow-up care. Subgingival plaque from the deepest pockets was recovered and assessed for bacterial content of Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans using the modified Invader PLUS assay. The corresponding serum IgG titers were measured using ELISA. Changes in clinical parameters were evaluated over the course of 24 months. The sensitivity, specificity, and prediction values were calculated and used to determine cutoff points for prediction of the progression of chronic periodontitis. RESULTS: Of the 124 individuals who completed the 24-month monitoring phase, 62 exhibited progression of periodontitis, whereas 62 demonstrated stable disease. The P. gingivalis counts of subgingival plaque from the deepest pockets was significantly associated with the progression of periodontitis (p < 0.001, positive predictive value = 0.708). CONCLUSIONS: The P. gingivalis counts of subgingival plaque from the deepest pockets may be associated with the progression of periodontitis.

DOI： 10.1186/s12903-017-0337-x

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歯周病対策としてのバイオフィルム制御の展望 Reviewed

高柴正悟

日本歯周病学会会誌 58 ( 4 ) 229 - 235 2017.1

Authorship：Lead author,　Corresponding author Language：Japanese Publisher：(NPO)日本歯周病学会

歯周病対策の基本である口腔細菌バイオフィルムの制御について概説した。バイオフィルムの形成は、細菌の初期付着、不可逆性付着、バイオフィルムの形成、増大と成熟、バイオフィルムからの細菌の分散、といった5段階であるとされる。バイオフィルムを形成すると、細菌間での情報交換であるquorum sensingが活発になり、浮遊状態である細菌の代謝活性とは異なるものになる。口腔に棲息する常在細菌叢を、質的に各細菌種の構成割合を維持し、一方で量的には各細菌種の細菌数を減少させることが,細菌と生体のバランスを考えると望ましいと考えられ、相利共生(symbiosis)の概念が普及してきた。また、細菌叢内でのquorum sensingを理解することで、細菌間での連携を攪乱する方法でバイオフィルムを阻止することも考えられている。

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Site-level progression of periodontal disease during a follow-up period Reviewed

Nomura, Y., Morozumi, T., Nakagawa, T., Sugaya, T., Kawanami, M., Suzuki, F., Takahashi, K., Abe, Y., Sato, S., Makino-Oi, A., Saito, A., Takano, S., Minabe, M., Nakayama, Y., Ogata, Y., Kobayashi, H., Izumi, Y., Sugano, N., Ito, K., Sekino, S., Numabe, Y., Fukaya, C., Yoshinari, N., Fukuda, M., Noguchi, T., Kono, T., Umeda, M., Fujise, O., Nishimura, F., Yoshimura, A., Hara, Y., Nakamura, T., Noguchi, K., Kakuta, E., Hanada, N., Takashiba, S., Amitani, Y., Yoshie, H.

PLoS ONE 12 ( 12 ) 2017

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

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 ) 2017

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

Ugawa, Y., Yamamoto, T., Kawamura, M., Yamashiro, K., Shimoe, M., Tomikawa, K., Hongo, S., Maeda, H., Takashiba, S.

Cell Biology International 41 ( 6 ) 2017

Salivary pathogen and serum antibody to assess the progression of chronic periodontitis: a 24-mo prospective multicenter cohort study Reviewed

Morozumi, T., Nakagawa, T., Nomura, Y., Sugaya, T., Kawanami, M., Suzuki, F., Takahashi, K., Abe, Y., Sato, S., Makino-Oi, A., Saito, A., Takano, S., Minabe, M., Nakayama, Y., Ogata, Y., Kobayashi, H., Izumi, Y., Sugano, N., Ito, K., Sekino, S., Numabe, Y., Fukaya, C., Yoshinari, N., Fukuda, M., Noguchi, T., Kono, T., Umeda, M., Fujise, O., Nishimura, F., Yoshimura, A., Hara, Y., Nakamura, T., Noguchi, K., Kakuta, E., Hanada, N., Takashiba, S., Yoshie, H.

Journal of Periodontal Research 51 ( 6 ) 768 - 778 2016.12

Smad2 overexpression enhances adhesion of gingival epithelial cells Reviewed

Hongo, S., Yamamoto, T., Yamashiro, K., Shimoe, M., Tomikawa, K., Ugawa, Y., Kochi, S., Ideguchi, H., Maeda, H., Takashiba, S.

Archives of Oral Biology 71 46 - 53 2016.11

The potential of positron emission tomography/computerized tomography (PET/CT) scanning as a detector of high-risk patients with oral infection during preoperative staging Reviewed

Yamashiro, K., Nakano, M., Sawaki, K., Okazaki, F., Hirata, Y., Takashiba, S.

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 122 ( 2 ) 242 - 249 2016.8

新たな糖尿病合併症に迫る糖尿病患者にとっての歯周病治療を再考する Reviewed

大森一弘, 高柴正悟

糖尿病合併症 30 ( 2 ) 198 - 201 2016.7

Effects of new over-the-counter periodontal ointment-containing applicator with single-tuft brush on cytokine levels in gingival crevicular fluid during supportive periodontal therapy phase: a randomized double-blind clinical trial. Reviewed International journal

K Takeuchi-Hatanaka, T Yasuda, Koji Naruishi, K Katsuragi-Fuke, J Inubushi, H Ootsuki, H Maeda, S Takashiba

Journal of Periodontal Research Vol.51 ( No.3 ) 321 - 331 2016.6

Synthetic terrein inhibits progression of head and neck cancer by suppressing angiogenin production Reviewed

Shibata, A., Ibaragi, S., M, ai, H., Tsumura, T., Kishimoto, K., Okui, T., Hassan, N.M.M., Shimo, T., Omori, K., Hu, G.-F., Takashiba, S., Suga, S., Sasaki, A.

Anticancer Research 36 ( 5 ) 2161 - 2168 2016.5

Randomized Placebo-Controlled and Controlled Non-Inferiority Phase III Trials Comparing Trafermin, a Recombinant Human Fibroblast Growth Factor 2, and Enamel Matrix Derivative in Periodontal Regeneration in Intrabony Defects Reviewed

Kitamura, M., Akamatsu, M., Kawanami, M., Furuichi, Y., Fujii, T., Mori, M., Kunimatsu, K., Shimauchi, H., Ogata, Y., Yamamoto, M., Nakagawa, T., Sato, S., Ito, K., Ogasawara, T., Izumi, Y., Gomi, K., Yamazaki, K., Yoshie, H., Fukuda, M., Noguchi, T., Takashiba, S., Kurihara, H., Nagata, T., Hamachi, T., Maeda, K., Yokota, M., Sakagami, R., Hara, Y., Noguchi, K., Furuuchi, T., Sasano, T., Imai, E., Ohmae, M., Koizumi, H., Watanuki, M., Murakami, S.

Journal of Bone and Mineral Research 31 ( 4 ) 806 - 814 2016.4

工藤値英子, 福家教子, 稗貫未希, 野呂泰子, 北條彩和子, 三辺正人, 児玉利朗, 高柴正悟

日本歯科保存学雑誌 59 ( 2 ) 178 - 186 2016.4

Authorship：Last author Language：Japanese Publisher：(NPO)日本歯科保存学会

目的:近年,口腔インプラント治療の増加に伴い,歯周病原細菌をはじめとする口腔細菌の感染症であるインプラント周囲炎が急増している.インプラント周囲炎は,口腔インプラントの予後を左右する主な因子の一つであり,細菌学的評価に基づいたインプラントを含む口腔内の感染管理の充実が求められる.そこでこのたび,歯周病原細菌関連検査におけるインプラント周囲炎の予測因子の有用性について検討した.方法:歯周病安定期治療あるいはインプラントリコール目的で受診中である,20歳以上の口腔インプラント治療歴があるメインテナンス患者5名(メインテナンス群)と,supportive periodontal therapy患者(SPT患者)10名(SPT群)を対象とした.対象の歯周ポケットとインプラント周囲ポケットの深さを測定し,パノラマX線写真から骨吸収がスクリューに及ぶインプラント(bone resoption in implant screw:BRIS)の有無を調査した.さらに,歯周病原細菌に対する血漿IgG抗体価検査と歯周病原細菌量の唾液検査(定量PCR法)を行った.得られたデータについて,メインテナンス群とSPT群間,BRIS非保有群とBRIS保有群間において統計学的に評価した.結果:BRIS保有患者数が,メインテナンス群よりもSPT群に有意に多かった.Porphyromonas. gingivalisに対する血漿IgG抗体価のcut-off値1.68を用いて陽性者と陰性者間で比較すると,抗体価の陽性者数がメインテナンス群よりSPT群に有意に多かった.また,唾液中の歯周病原細菌検出者数をメインテナンス群とSPT群間で比較したところ,唾液中のTannerella forsythiaの保菌者がメインテナンス群よりSPT群に有意に多かった.さらに,歯周病原細菌に対する血漿IgG抗体価と唾液中の歯周病原細菌検出者数をBRIS非保有群とBRIS保有群間で比較した.その結果,P.gingivalisに対する血漿IgG抗体価の陽性者数と唾液中のT.forsythiaの保菌者が,BRIS非保有群よりBRIS保有群に有意に多かった.結論:血液と唾液を用いた歯周病原細菌関連検査が,インプラント周囲炎の予測因子として有用である可能性が示唆された.(著者抄録)

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Papers - TAKASHIBA Shogo