研究者基本情報

• 博士(歯学), 北海道大学, 2017年03月

• https://researchmap.jp/19820703

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201701019772631166
• https://orcid.org/0000-0001-9412-1986

• 10759202

• https://orcid.org/0000-0001-9412-1986

• 201701019772631166

• ライフサイエンス, 生理学
• ライフサイエンス, 口腔再生医学、歯科医用工学
• ライフサイエンス, 免疫学, 分子生物学

• 修士課程, 総合化学院
• 博士課程, 総合化学院

研究活動情報

• 2024年09月, 北海道大学遺伝子病制御研究所, 第10回北海道大学部局横断シンポジウム 奨励賞
  色素産生細胞のメラニン産生機構が自然免疫担当分子SCI23を介して 炎症応答を制御するメカニズムの解析
  鈴木 啓;佐藤 精一;武藤 ひなの;大久保 葵;櫻井 希;髙岡晃教
• 2018年10月, 第40回リバネス研究費池田理化再生医療研究奨励賞
  質量分析装置を用いた、骨組織における外力検知機構およびその化学的シグナル分子の探索と解析
  鈴木 啓

• 17β-Estradiol (E2) Activates Matrix Mineralization through Genomic/Nongenomic Pathways in MC3T3-E1 Cells
  Hiraku Suzuki; Yuki Fujiwara; Winda Ariyani; Izuki Amano; Sumiyasu Ishii; AYANE NINOMIYA; Seiichi Sato; Akinori Takaoka; Noriyuki Koibuchi
  International Journal of Molecular Sciences, 25, 9, 4727, 2024年04月26日, ［査読有り］, ［筆頭著者］
  英語, 研究論文（学術雑誌）, Estrogen plays an important role in osteoporosis prevention. We herein report the possible novel signaling pathway of 17β-estradiol (E2) in the matrix mineralization of MC3T3-E1, an osteoblast-like cell line. In the culture media-containing stripped serum, in which small lipophilic molecules such as steroid hormones including E2 were depleted, matrix mineralization was significantly reduced. However, the E2 treatment induced this. The E2 effects were suppressed by ICI182,780, the estrogen receptor (ER)α, and the ERβ antagonist, as well as their mRNA knockdown, whereas Raloxifene, an inhibitor of estrogen-induced transcription, and G15, a G-protein-coupled estrogen receptor (GPER) 1 inhibitor, had little or no effect. Furthermore, the E2-activated matrix mineralization was disrupted by PMA, a PKC activator, and SB202190, a p38 MAPK inhibitor, but not by wortmannin, a PI3K inhibitor. Matrix mineralization was also induced by the culture media from the E2-stimulated cell culture. This effect was hindered by PMA or heat treatment, but not by SB202190. These results indicate that E2 activates the p38 MAPK pathway via ERs independently from actions in the nucleus. Such activation may cause the secretion of certain signaling molecule(s), which inhibit the PKC pathway. Our study provides a novel pathway of E2 action that could be a therapeutic target to activate matrix mineralization under various diseases, including osteoporosis.
• Lactational exposure to perfluorooctane sulfonate remains a potential risk in brain function of middle-aged male mice
  Ayane Ninomiya; Izuki Amano; Hiraku Suzuki; Yuki Fujiwara; Asahi Haijima; Noriyuki Koibuchi
  The Journal of Physiological Sciences, 74, 1, Springer Science and Business Media LLC, 2024年03月05日
  研究論文（学術雑誌）, Abstract
  
  Perfluorooctane sulfonate (PFOS) exerts adverse effects on neuronal development in young population. Limited evidences have shown that early-life PFOS exposure holds a potential risk for developing age-related neurodegenerative diseases such as Alzheimer’s disease later in life. The present study investigated the effects of lactational PFOS exposure on cognitive function using one-year-old mice. Dams were exposed to PFOS (1 mg/kg body weight) through lactation by gavage. Male offspring were used for the behavior test battery to assess cognitive function. Western blot analysis was conducted to measure the levels of proteins related to the pathogenesis of Alzheimer’s disease. PFOS-exposed mice displayed a mild deficiency in social recognition. In the hippocampus, the expression of tau protein was significantly increased. These results underline a mild effect of developing PFOS exposure on cognitive function and neurodegeneration. The present study presents the long-lasting effects of PFOS in middle-aged period and warrants a potential aftermath.
• 細胞外脂質シグナルを介した骨芽細胞のメカノストレスの細胞外伝播機構
  鈴木 啓, 佐藤精一, 鯉淵典之
  アレルギーの臨床, 43, 11, 57, 62, 2023年10月, ［筆頭著者, 責任著者］
  日本語
• 骨組織のメカニカルストレス伝播機構
  鈴木 啓, 佐藤精一, 鯉淵典之
  BIO Clinica, 38, 4, 67, 72, 2023年04月, ［筆頭著者, 責任著者］
  日本語, 研究論文（学術雑誌）, 37039165
• The role of autonomously secreted PGE2 and its autocrine/paracrine effect on bone matrix mineralization at the different stages of differentiating MC3T3-E1 cells
  Hiraku Suzuki; Noriyasu Ohshima; Kazuaki Tatei; Tomoyo Taniguchi; Seiichi Sato; Takashi Izumi
  Biochemical and Biophysical Research Communications, 524, 4, 929, 935, Elsevier {BV}, 2020年04月, ［査読有り］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）, Bone is consisted of osteoblast-linage cells, bone-forming cells in various differentiation stages. However, it is not fully understood how communicate and interact these cells immigrated from bone marrow. In this study, we showed that prostaglandin E2 (PGE2) had a role in autonomous modification of matrix mineralization in osteoblastic cell line, MC3T3-E1, and interactions across the cells in different differ- entiation stages.
  Analysis using LC-MS/MS and inhibitors showed the autonomous secretion of PGE2 among the pros- tanoids in differentiation stages and that depend on COX-2, a key enzyme for production of PGE2. Treatment with inhibitors of PGE2 receptors and COX-2 indicated that secreted PGE2 regulates matrix mineralization in an autocrine/paracrine manner. In addition, we showed that the expression profile of PGE2 receptors (EP1-EP4) and PGE2 effects on matrix mineralization derived from it changed during cell differentiation.
  Treatment with inhibitors of PGE2 signaling in the early differentiation stage of MC3T3-E1 cells induced significant changes in matrix mineralization several days after. Stimulation with the extracts from culture medium of the matured cells including PGE2 and co-culture with the matured cells secreting PGE2 significantly promoted matrix mineralization of the early stage cells, in contrast, treat- ment with inhibitor of COX-2 and PGE2 receptors failed to do so. These results support that PGE2 plays important roles in the interaction system of osteoblast-linage cells in bone tissue to regulate matrix mineralization reflecting condition of bone-forming cells, that is, population and maturation.
• Regulation of MC3T3-E1 differentiation by actin cytoskeleton through lipid mediators reflecting the cell differentiation stage.
  Hiraku Suzuki; Kazuaki Tatei; Noriyasu Ohshima; Seiichi Sato; Takashi Izumi
  Biochemical and biophysical research communications, 514, 2, 393, 400, Elsevier {BV}, 2019年06月25日, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Actin cytoskeleton is reported to be related in various functions of osteoblast, bone-forming cell. However the function of actin cytoskeleton in osteoblasts is not fully understood, since bone formation is derived from extracellular interactions of functional proteins produced from osteoblasts, including osteocalcin (Ocn), and it is a result of closely and complex organized sequence of biochemical events. In this study, we showed that actin cytoskeleton of MC3T3-E1 cells functioned in recognition of cell condition and regulation of extracellular matrix mineralization, bone formation. Maturation of MC3T3-E1 cells by 14 days of culture reduced F-actin filaments, while induced expression of Ocn mRNA known as late stage differentiation marker and matrix mineralization, terminal stage of cell differentiation. The disruption of actin cytoskeleton with Cyto D in immature MC3T3-E1 cells significantly increased expression of Ocn mRNA in 24 h. Both PTX-induced inhibition of signal transduction through GPCRs and celecoxib-induced suppression of lipid mediators in immature MC3T3-E1 cells reduced actin filaments and suppressed matrix mineralization. Furthermore, addition of lipid mediators extracted from culture mediums of differentiated MC3T3-E1 cells by Bligh-Dyer method induced actin cytoskeleton reorganization and matrix mineralization change in MC3T3-E1 cells. Taken together, our data suggest that actin cytoskeleton of MC3T3-E1 cells regulates activation of developmental pathway reflecting cell differentiation stages through lipid mediators. The function we identified is important for bone formation tightly regulated by mechanical stress, since actin cytoskeleton is also known as a mechanosensor of osteoblasts.
• BinCARD2 as a positive regulator of interferon response in innate immunity
  Hiraku Suzuki; Takeshi Kameyama; Akinori Takaoka
  Biochemical and Biophysical Research Communications, 511, 2, 287, 293, Elsevier {BV}, 2019年04月, ［査読有り］, ［筆頭著者, 責任著者］
  英語, 研究論文（学術雑誌）, Innate immunity is a system that recognizes primarily and excludes pathogenic microorganism. MAVS/ IPS-1/Cardif/Visa functions as an adapter protein for RIG-I like receptors (RLRs) and plays a key role in the production of antiviral proteins, interferons (IFNs), for RNA viruses. However, the activation mechanism is not fully understood. Here, we show that BinCARD isoform2 (BinCARD2), carrying CARD domain structure like MAVS, functions in innate immune response. Knockdown of BinCARD2 reduced the RLR ligand-induced expression of IFN-b mRNA and activation of the IFNB promoter. The activation of the IFNB promoter by overexpression of MAVS or TBK1 was suppressed by silencing of BinCARD2, but no effect on IFNB promoter activation by overexpression of TRIF or constitutive activated IRF-3. Furthermore, we confirmed that BinCARD2 protein associated with MAVS but not TBK1 by immunoprecipitation and colocalized with MAVS. Accordingly, we investigated whether BinCARD2 was involved in MAVS activa- tion and showed that siBinCARD2 did not affect RIG-I/MAVS binding but impaired the MAVS oligo- merization. Moreover, we infected A549cells with vesicular stomatitis virus (VSV) and found that induction of IFN-b and IL-6 mRNA after VSV infection was decreased by BinCARD2 knockdown. Thus, these data may suggest that BinCARD2 associates with MAVS to positively modulate the oligomerization in the RIG-I like receptors pathway and activates innate immune response.
• Osteoblast Differentiation Is Functionally Associated With Decreased AMP Kinase Activity
  Takayuki Kasai; Kenjiro Bandow; Hiraku Suzuki; Norika Chiba; Kyoko Kakimoto; Tomokazu Ohnishi; Shin-Ichiro Kawamoto; Eiichi Nagaoka; Tetsuya Matsuguchi
  JOURNAL OF CELLULAR PHYSIOLOGY, 221, 3, 740, 749, 2009年12月, ［査読有り］
  英語, 研究論文（学術雑誌）

• コロナ禍におけるオンライン併用生理学実習
  藤原 悠基; 天野 出月; 石井 角保; 鈴木 啓; 岸 美紀子; 鯉淵 典之, 医学教育, 52, Suppl., 153, 153, 2021年07月
  (一社)日本医学教育学会, 日本語
• 膜貫通型リゾホスホリパーゼD、GDE4過剰発現細胞における脂質の網羅的解析
  大嶋 紀安; 荒木 麻理; 大日方 英; 小西 昭充; 鈴木 啓; 立井 一明; 和泉 孝志, 生命科学系学会合同年次大会, 2017年度, [2P, 0027], 2017年12月
  生命科学系学会合同年次大会運営事務局, 日本語
• 骨芽細胞様細胞MC3T3-E1における分化段階に応じた機械的刺激による骨形成制御応答の解析
  鈴木 啓; 大嶋 紀安; 小西 昭充; 立井 一明; 佐藤 精一; 和泉 孝志, 生命科学系学会合同年次大会, 2017年度, [2P, 0735], 2017年12月
  生命科学系学会合同年次大会運営事務局, 日本語

• 機械的刺激受容体Piezo1の活性化は骨芽細胞様細胞株M.;E;のエストロゲン応答と骨化を抑制する
  鈴木啓
  第66回歯科基礎医学会学術大会, 2024年11月04日, 日本語, 口頭発表（一般）
  2024年11月02日 - 2024年11月04日
• 骨芽細胞様細胞株MC3T3-E1におけるPGE2分泌を介したメカノストレス伝播機構の解析
  鈴木啓; 髙岡晃教; 和泉孝志
  第65回脂質生化学会, 2023年06月08日, 日本語, 口頭発表（一般）
  2023年06月08日 - 2023年06月09日, 37039165
• エストロゲンの超低濃度環境下において、エストラジオールは骨形成細胞 株MC3T3-E1の分化と基質石灰化のトリガーとなる
  鈴木 啓
  第99回 日本生理学会大会, 2022年03月17日, 英語
  2022年03月16日 - 2022年03月18日
• 機械的刺激応答研究に適した実験用骨組織の構築と、それを介在する非タンパク性分子による制御機構の解明
  鈴木 啓
  第8回 超異分野学会, 2019年03月08日, 日本語, 口頭発表（一般）
  ［招待講演］, ［国内会議］

  
  発表資料

• 2020年10月 - 現在
  日本生理学会
• 2018年07月 - 現在
  日本医学教育学会
• 超異分野学会
• 日本脂質生化学会
• 日本分子生物学会

• 脂質シグナルに着目した骨組織のメカニカルストレス応答性骨形成制御機構の解析
  科学研究費助成事業 若手研究
  2021年04月 - 2023年03月
  鈴木 啓
  本研究は骨組織のメカニカルストレス(機械的刺激)応答性骨形態制御における、脂質シグナル分子による細胞間情報伝達機構の解明を目指すものである。このため、2021年度では1) 骨芽細胞様細胞株のMS応答性脂質シグナル分子の探索と解析、2) 骨芽細胞様細胞株においてMS応答反応を伝達する脂質シグナル分子の同定の2つを目標に、短時間の機械的刺激によって放出される脂質シグナル分子の特定と、測定に適した条件の探索を行った。
  我々は本研究に適した、一時的かつ強い荷重条件を設定するため、補助金を用いて細胞株、専用の遠心分離機スウィングローターおよび候補シグナル分子のELISA kitを購入し、様々な条件下で、細胞培養液中の脂質シグナル分子量が放出される条件の検討を行った。結果として、特定の細胞形態および分化段階において刺激前後の培養液中のシグナル分子量が変動すること、分化制御に関与する細胞培養液中のシグナル分子の有無によって、この変化が劇的に増大することを見出している。また、この脂質シグナル分子放出量の変化に関与するシグナル分子は機械的刺激と無関係に様々な分化制御に関与していることも我々は確認しており、その関連についても検討中である。
  また一方で、シグナル分子の放出に適した条件と、シグナル分子の受容とそれによる分化制御に適した条件が異なっていることを見出しつつあり、細胞培養液を介した細胞間シグナル応答解析用の実験系の確立も含め、更なる解析を進めている。
  日本学術振興会, 若手研究, 群馬大学, 研究代表者, 21K15341