研究者詳細 - 秋山　謙太郎

論文 - 秋山　謙太郎

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Implant-supported fixed prostheses with cantilever: a systematic review and meta-analysis. 査読国際誌

Yusuke Kondo, Kiyoshi Sakai, Hajime Minakuchi, Takuya Horimai, Takuo Kuboki, JSOI Clinical Guideline Working, Group collaborators, Ikiru Atsuta, Kazuki Takaoka, Norimasa Tanabe, Akira Hasuike, Kensuke Yamauchi, Aita Hideki, Kentaro Akiyama, Yasunori Ayukaw, Masamitsu Oshima, Yoko Kurosaki, Yohei Sato, Kazuhiko Hiroyasu, Junichi Furuya, Takuya Mino, Takashi Sakamoto, Hisatomo Kondo, Takashi Miyazaki, Ryuji Hosokaw

International journal of implant dentistry 10 ( 1 ) 57 - 57 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: This systematic review (SR) aimed to investigate whether the presence of a cantilever affects the results of implant treatment for partial edentulism, including an analysis of the anterior and posterior regions of the dental arches. METHODS: An electronic search was performed, and original articles published between 1995 and November 2023 were included. The outcomes were the implant survival rate, patient satisfaction, occurrence of mechanical complications, and marginal bone loss around the implants. Two SR members independently examined the validity of the studies, extracted evidence from the included studies, and performed risk of bias assessment, comprehensive evidence evaluation, and meta-analysis. RESULTS: Nine studies met our inclusion criteria. Implant survival rate tended to be lower in the cantilever group, and marginal bone loss tended to be higher in the cantilever group; however, there was no significant difference. There was no significant difference in patient satisfaction based on the presence or absence of a cantilever. Moreover, the incidence of mechanical complications was significantly higher in the cantilever group. According to the analysis of anterior and posterior regions, implant survival rate tended to be lower in the cantilever group of the posterior region, and marginal bone loss around the implants tended to be higher in the cantilever group of the anterior region. CONCLUSION: Implant-supported fixed prostheses with cantilevers did not negatively affect implant survival rate, marginal bone loss, or patient satisfaction. However, the incidence of mechanical complications significantly increased in the cantilever group.

DOI： 10.1186/s40729-024-00573-8

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Macrophages modulate mesenchymal stem cell function via tumor necrosis factor alpha in tooth extraction model. 国際誌

Aung Ye Mun, Kentaro Akiyama, Ziyi Wang, Jiewen Zhang, Wakana Kitagawa, Teisaku Kohno, Ryuji Tagashira, Kei Ishibashi, Naoya Matsunaga, Tingling Zou, Mitsuaki Ono, Takuo Kuboki

JBMR plus 8 ( 8 ) ziae085 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Mesenchymal stem cells (MSCs) and macrophages collaboratively contribute to bone regeneration after injury. However, detailed mechanisms underlying the interaction between MSCs and inflammatory macrophages (M1) remain unclear. A macrophage-depleted tooth extraction model was generated in 5-wk-old female C57BL/6J mice using clodronate liposome (12.5 mg/kg/mouse, intraperitoneally) or saline injection (control) before maxillary first molar extraction. Mice were sacrificed on days 1, 3, 5, 7, and 10 after tooth extraction (n = 4). Regenerated bone volume evaluation of tooth extraction socket (TES) and histochemical analysis of CD80+M1, CD206+M2 (anti-inflammatory macrophages), PDGFRα+MSC, and TNF-α+ cells were performed. In vitro, isolated MSCs with or without TNF-α stimulation (10 ng/mL, 24 h, n = 3) were bulk RNA-sequenced (RNA-Seq) to identify TNF-α stimulation-specific MSC transcriptomes. Day 7 micro-CT and HE staining revealed significantly lower mean bone volume (clodronate vs control: 0.01 mm3 vs 0.02 mm3, p<.0001) and mean percentage of regenerated bone area per total TES in clodronate group (41.97% vs 54.03%, p<.0001). Clodronate group showed significant reduction in mean number of CD80+, TNF-α+, PDGFRα+, and CD80+TNF-α+ cells on day 5 (306.5 vs 558.8, p<.0001; 280.5 vs 543.8, p<.0001; 365.0 vs 633.0, p<.0001, 29.0 vs 42.5, p<.0001), while these cells recovered significantly on day 7 (493.3 vs 396.0, p=.0004; 479.3 vs 384.5, p=.0008; 593.0 vs 473.0, p=.0010, 41.0 vs 32.5, p=.0003). RNA-Seq analysis showed that 15 genes (|log2FC| > 5.0, log2TPM > 5) after TNF-α stimulation were candidates for regulating MSC's immunomodulatory capacity. In vivo, Clec4e and Gbp6 are involved in inflammation and bone formation. Clec4e, Gbp6, and Cxcl10 knockdown increased osteogenic differentiation of MSCs in vitro. Temporal reduction followed by apparent recovery of TNF-α-producing M1 macrophages and MSCs after temporal macrophage depletion suggests that TNF-α activated MSCs during TES healing. In vitro mimicking the effect of TNF-α on MSCs indicated that there are 15 candidate MSC genes for regulation of immunomodulatory capacity.

DOI： 10.1093/jbmrpl/ziae085

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Age-Related Effects on MSC Immunomodulation, Macrophage Polarization, Apoptosis, and Bone Regeneration Correlate with IL-38 Expression. 国際誌

Jiewen Zhang, Kentaro Akiyama, Aung Ye Mun, Ryuji Tagashira, Tingling Zou, Naoya Matsunaga, Teisaku Kohno, Takuo Kuboki

International journal of molecular sciences 25 ( 6 ) 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Mesenchymal stem cells (MSCs) are known to promote tissue regeneration and suppress excessive inflammation caused by infection or trauma. Reported evidence indicates that various factors influence the expression of MSCs' endogenous immunomodulatory properties. However, the detailed interactions of MSCs with macrophages, which are key cells involved in tissue repair, and their regulatory mechanisms are not completely understood. We herein investigated how age-related immunomodulatory impairment of MSCs alters the interaction of MSCs with macrophages during bone healing using young (5-week old) and aged (50-week old) mice. To clarify the relationship between inflammatory macrophages (M1) and MSCs, their spatiotemporal localization at the bone healing site was investigated by immunostaining, and possible regulatory mechanisms were analyzed in vitro co-cultures. Histomorphometric analysis revealed an accumulation of M1 and a decrease in MSC number at the healing site in aged mice, which showed a delayed bone healing. In in vitro co-cultures, MSCs induced M1 apoptosis through cell-to-cell contact but suppressed the gene expression of pro-inflammatory cytokines by soluble factors secreted in the culture supernatant. Interestingly, interleukin 38 (Il-38) expression was up-regulated in M1 after co-culture with MSCs. IL-38 suppressed the gene expression of inflammatory cytokines in M1 and promoted the expression of genes associated with M1 polarization to anti-inflammatory macrophages (M2). IL-38 also had an inhibitory effect on M1 apoptosis. These results suggest that MSCs may induce M1 apoptosis, suppress inflammatory cytokine production by M1, and induce their polarization toward M2. Nevertheless, in aged conditions, the decreased number and immunomodulatory function of MSCs could be associated with a delayed M1 clearance (i.e., apoptosis and/or polarization) and consequent delayed resolution of the inflammatory phase. Furthermore, M1-derived IL-38 may be associated with immunoregulation in the tissue regeneration site.

DOI： 10.3390/ijms25063252

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卒前臨床技術教育でデジタル光学印象を経験させる相互実習の導入

下村侑司, 土山雄司, 窪木慎野介, 松永直也, 北川若奈, 黄野頂策, 石橋啓, 田仲由希恵, 大森江, 水口真実, 中川晋輔, 三木春奈, 三野卓哉, 前田あずさ, 縄稚久美子, 秋山謙太郎, 水口一, 窪木拓男

岡山歯学会雑誌 41 ( 2 ) 58 - 59 2022年12月

Therapeutic effects of peptide P140 in a mouse periodontitis model. 国際誌

Kentaro Akiyama, Kyaw Thu Aung, Laura Talamini, Olivier Huck, Takuo Kuboki, Sylviane Muller

Cellular and molecular life sciences : CMLS 79 ( 10 ) 518 - 518 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

In our search for innovative drugs that could improve periodontal treatment outcomes, autophagy and its anomalies represent a potential target for therapeutic intervention. We sought to identify autophagy defects in murine experimental periodontitis and study the effectiveness of P140, a phosphopeptide known to bind HSPA8 and inhibit its chaperone properties, and that corrects autophagy dysfunctions in several autoimmune and inflammatory diseases. Experimental periodontitis was induced by placing silk ligature around mandibular first molars. Sick mice were treated intraperitoneally with either P140 or a control, scrambled peptide. After 10 days, mandibles were harvested and bone loss was measured by micro-CT. Immune cells infiltration was studied by histological analyses. Cytokines levels and autophagy-related markers expression were evaluated by qRT-PCR and western blotting. A comparison with non-affected mice revealed significant alterations in the autophagy processes in mandibles of diseased mice, especially in the expression of sequestosome 1/p62, Maplc3b, Atg5, Ulk1, and Lamp2. In vivo, we showed that P140 normalized the dysregulated expression of several autophagy-related genes. In addition, it diminished the infiltration of activated lymphocytes and pro-inflammatory cytokines. Unexpectedly P140 decreased the extent of bone loss affecting the furcation and alveolar areas. Our results indicate that P140, which was safe in clinical trials including hundreds of autoimmune patients with systemic lupus erythematosus, not only decreases the inflammatory effects observed in mandibular tissues of ligation-induced mice but strikingly also contributes to bone preservation. Therefore, the therapeutic peptide P140 could be repositioned as a decisive breakthrough for the future therapeutic management of periodontitis.

DOI： 10.1007/s00018-022-04537-2

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間葉系幹細胞とM1,M2マクロファージの間接的相互作用による骨再生

田頭龍二, 黄野頂策, 秋山謙太郎, 窪木拓男

日本口腔インプラント学会誌 35 ( 特別号 ) O - 12 2022年9月

院内で完結する補綴主導口腔インプラント手術のための汎用デジタルワークフロー

大國峻, 坂本和基, 北川若奈, 下村侑司, 松永直也, 三野卓哉, 秋山謙太郎, 清水浩明, 前川賢治, 窪木拓男

日本補綴歯科学会誌 14 ( 中国・四国支部学術大会特別号 ) 27 - 27 2022年8月

院内で完結する補綴主導口腔インプラント手術のための汎用デジタルワークフロー

大國峻, 坂本和基, 北川若奈, 下村侑司, 松永直也, 三野卓哉, 秋山謙太郎, 清水浩明, 前川賢治, 窪木拓男

日本補綴歯科学会誌 14 ( 中国・四国支部学術大会特別号 ) 27 - 27 2022年8月

創傷治癒過程における間葉系幹細胞とマクロファージの相互作用

田頭龍二, 黄野頂策, 秋山謙太郎, 窪木拓男

日本補綴歯科学会誌 14 ( 特別号 ) 179 - 179 2022年7月

加齢が骨髄ニッチ関連細胞および類洞基底膜に与える影響

石橋啓, 大野充昭, 土佐郁恵, 北川若奈, 秋山謙太郎, 窪木拓男, 大橋俊孝

日本補綴歯科学会誌 14 ( 特別号 ) 148 - 148 2022年7月

【インプラント治療の症型分類】エビデンスに基づいたインプラント治療難易度診断ツールの開発

鮎川保則, 會田英紀, 秋山謙太郎, 大島正充, 佐藤洋平, 廣安一彦, 古屋純一, 山田陽一, 澤瀬隆, 窪木拓男

日本口腔インプラント学会誌 35 ( 2 ) 83 - 91 2022年6月

記述言語：日本語出版者・発行元：(公社)日本口腔インプラント学会

本邦では口腔外科や補綴,歯周病のいずれかに軸足を置く歯科医師がインプラント治療を担当することが多いように思われる.そのため,特に自身がメインフィールドとする領域以外の治療において正確な難易度を判定する手法があれば,安心安全なインプラント治療を提供することができると考えられる.現在,いくつかのインプラント治療難易度判定ツールが提案されているが,これまでに用いられてきた種々の分類法では難易度をうまく表現できない問題も存在する.たとえば,骨の質,量ともに問題なく咬合にも問題ない下顎臼歯部1歯中間欠損などはイージーケースといっても差し支えないと思われるが,一方で未経験者にとっては,骨をドリリングすること自体が難しく感じられるだろう.このように,ある症例が簡単か難しいかは,術者の感じ方や経験で大きく異なる.また,このような術者間で感じ方に差がある技術的難易度とは別個に,全身状態や治療部位,患者の個性に基づく難易度が存在する.これらの項目に問題がある場合にインプラント治療の成功率が低下することは,多くの場合質が高いエビデンスで裏づけされている.日本口腔インプラント学会研究推進委員会では,Evidence-Based Difficulty Assessment Toolともいえる,術者の経験によらないインプラント治療の難易度分類を試みている.本稿ではその試案を提示する.(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J02151&link_issn=&doc_id=20220801250004&doc_link_id=10.11237%2Fjsoi.35.83&url=https%3A%2F%2Fdoi.org%2F10.11237%2Fjsoi.35.83&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

インプラント治療は高齢者の残存歯を守りQOLを高めるか?

窪木拓男, 黒崎陽子, 大野彩, 三野卓哉, 荒川光, 小山絵理, 中川晋輔, Ha Thi Thu Nguyen, 逢坂卓, 佐伯真未子, 水口一, 大野充昭, 前川賢治, 會田英紀, 澤瀬隆, 鮎川保則, 秋山謙太郎, 大島正充, 佐藤裕二, 佐藤洋平, 廣安一彦, 山田陽一, 阪本貴司, 宮崎隆, 日本口腔インプラント学会研究推進委員会

8020: はち・まる・にい・まる 2020 ( 21 ) 153 - 155 2022年2月

記述言語：日本語出版者・発行元：(公財)8020推進財団

インプラント治療後の残存歯および口腔関連QOLを他の歯科補綴治療との比較から明らかにすることを目的に、過去にインプラント義歯(IP)、ブリッジ(BR)、床義歯(RPD)治療前後に口腔関連QOL評価を受けた患者105名(IP群58名、BR群27名、RPD群20名)を対象に、6年経過後の追跡調査時における対象補綴装置の6年累積生存率、残存歯数、および口腔関連QOLを評価した。その結果、6年累積生存率はIP群94.7%、BR群77.4%、RPD群33.3%で、IP群は他の2群に比べ有意に高かった。追跡調査時の残存歯数については、IP群がRPD群に比べ有意に多かった。また、口腔関連QOLについては、IP群では治療開始前後、および治療前・追跡調査時のいずれにおいても有意に高くなっていたのに対し、他の2群ではいずれも有意差は認めなかった。

J-GLOBAL

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口腔インプラントの補綴主導型デジタルシミュレーションを確実に一次手術に反映する新しいワークフロー

北川若奈, 坂本和基, 大國峻, 下村侑司, 松永直也, 三野卓哉, 秋山謙太郎, 前川賢治, 窪木拓男

日本補綴歯科学会誌 13 ( 中国・四国支部学術大会特別号 ) 12 - 12 2021年8月

Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo. 国際誌

Hai Thanh Pham, Mitsuaki Ono, Emilio Satoshi Hara, Ha Thi Thu Nguyen, Anh Tuan Dang, Hang Thuy Do, Taishi Komori, Ikue Tosa, Yuri Hazehara-Kunitomo, Yuya Yoshioka, Yasutaka Oida, Kentaro Akiyama, Takuo Kuboki

Materials (Basel, Switzerland) 14 ( 1 ) 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Aging tissues present a progressive decline in homeostasis and regenerative capacities, which has been associated with degenerative changes in tissue-specific stem cells and stem cell niches. We hypothesized that amino acids could regulate the stem cell phenotype and differentiation ability of human bone marrow-derived mesenchymal stromal cells (hBMSCs). Thus, we performed a screening of 22 standard amino acids and found that D-tryptophan (10 μM) increased the number of cells positive for the early stem cell marker SSEA-4, and the gene expression levels of OCT-4, NANOG, and SOX-2 in hBMSCs. Comparison between D- and L-tryptophan isomers showed that the latter presents a stronger effect in inducing the mRNA levels of Oct-4 and Nanog, and in increasing the osteogenic differentiation of hBMSCs. On the other hand, L-tryptophan suppressed adipogenesis. The migration and colony-forming ability of hBMSCs were also enhanced by L-tryptophan treatment. In vivo experiments delivering L-tryptophan (50 mg/kg/day) by intraperitoneal injections for three weeks confirmed that L-tryptophan significantly increased the percentage of cells positive for SSEA-4, mRNA levels of Nanog and Oct-4, and the migration and colony-forming ability of mouse BMSCs. L-kynurenine, a major metabolite of L-tryptophan, also induced similar effects of L-tryptophan in enhancing stemness and osteogenic differentiation of BMSCs in vitro and in vivo, possibly indicating the involvement of the kynurenine pathway as the downstream signaling of L-tryptophan. Finally, since BMSCs migrate to the wound healing site to promote bone healing, surgical defects of 1 mm in diameter were created in mouse femur to evaluate bone formation after two weeks of L-tryptophan or L-kynurenine injection. Both L-tryptophan and L-kynurenine accelerated bone healing compared to the PBS-injected control group. In summary, L-tryptophan enhanced the stemness and osteoblastic differentiation of BMSCs and may be used as an essential factor to maintain the stem cell properties and accelerate bone healing and/or prevent bone loss.

DOI： 10.3390/ma14010208

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Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model. 国際誌

Kyaw Thu Aung, Kentaro Akiyama, Masayoshi Kunitomo, Aung Ye Mun, Ikue Tosa, Ha Thi Thu Nguyen, Jiewen Zhang, Teisaku Kohno, Mitsuaki Ono, Emilio Satoshi Hara, Takuo Kuboki

International journal of molecular sciences 21 ( 21 ) 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor α (PDGFRα)+ MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated β galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration.

DOI： 10.3390/ijms21218103

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口腔インプラント治療に対するカダバー外科トレーニングの取り組み

大野充昭, 秋山謙太郎, 三野卓哉, 大野彩, 水口一, 黒崎陽子, 園山亘, 窪木拓男

日本口腔インプラント学会誌 33 ( 特別号 ) 423 - 423 2020年9月

Ammonium tetrathiomolybdate enhances the antitumor effect of cisplatin via the suppression of ATPase copper transporting beta in head and neck squamous cell carcinoma. 査読国際誌

Shoji Ryumon, Tatsuo Okui, Yuki Kunisada, Koji Kishimoto, Tsuyoshi Shimo, Kazuaki Hasegawa, Soichiro Ibaragi, Kentaro Akiyama, Nguyen Thi Thu Ha, Nur Mohammad Monsur Hassan, Akira Sasaki

Oncology reports 42 ( 6 ) 2611 - 2621 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Platinum‑based antitumor agents have been widely used to treat head and neck squamous cell carcinoma (HNSCC) and numerous other malignancies. Cisplatin is the most frequently used platinum‑based antitumor agent, however drug resistance and numerous undesirable side effects limit its clinical efficacy for cancer patients. Cancer cells discharge cisplatin into the extracellular space via copper transporters such as ATPase copper transporting beta (ATP7B) in order to escape from cisplatin‑induced cell death. In the present study, it was demonstrated for the first time that the copper chelator ammonium tetrathiomolybdate (TM) has several promising effects on cisplatin and HNSCC. First, TM suppressed the ATP7B expression in HNSCC cell lines in vitro, thereby enhancing the accumulation and apoptotic effect of cisplatin in the cancer cells. Next, it was revealed that TM enhanced the antitumor effect of cisplatin in HNSCC cell tumor progression in a mouse model of bone invasion, which is important since HNSCC cells frequently invade to facial bone. Finally, it was demonstrated that TM was able to overcome the cisplatin resistance of a human cancer cell line, A431, via ATP7B depression in vitro.

DOI： 10.3892/or.2019.7367

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骨髄環境におけるBMP-2誘導性骨形成・骨芽細胞分化抑制メカニズムの解明

納所秋二, 大野充昭, Nguyen Ha, 笈田育尚, 小盛大志, 秋山謙太郎, 大橋俊孝, 窪木拓男

日本補綴歯科学会誌 11 ( 特別号 ) 130 - 130 2019年5月

抗Dickkopf1(DKK-1)抗体による骨分化能メカニズムの解明

井上美穂, ラジュ・レスミ, 岩浅匠真, 秋山謙太郎, 大島正充, 窪木拓男, 松香芳三

日本補綴歯科学会誌 11 ( 特別号 ) 301 - 301 2019年5月

Acidic Pre-Conditioning Enhances the Stem Cell Phenotype of Human Bone Marrow Stem/Progenitor Cells 査読

Yuri Hazehara-Kunitomo, Emilio Hara, Mitsuaki Ono, Kyaw Thu Aung, Keiko Komi, Hai Thanh Pham, Kentaro Akiyama, Masahiro Okada, Toshitaka Oohashi, Takuya Matsumoto, Takuo Kuboki

International Journal of Molecular Sciences 20 ( 5 ) 2019年3月

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