依田 昌樹 (ヨダ マサキ)

YODA Masaki

写真a

所属(所属キャンパス)

医学部 整形外科学教室 (信濃町)

職名

特任助教(有期)

外部リンク

経歴 【 表示 / 非表示

  • 2019年04月
    -
    継続中

    慶應義塾大学, 医学部 整形外科学, 特任助教

  • 2016年04月
    -
    2019年03月

    慶應義塾大学, 医学部 共同利用研究室 細胞組織学研究室, 助教

  • 2007年01月
    -
    2016年03月

    慶應義塾大学, 医学部 抗加齢運動器楽寄付講座(整形外科学), 特任助教

学歴 【 表示 / 非表示

  • 1997年04月
    -
    2003年03月

    東北大学, 農学研究科, 資源生物科学専攻

    日本, 大学院, 修了, 博士後期

学位 【 表示 / 非表示

  • 博士(農学), 東北大学, 課程, 2003年03月

    サケ科魚類におけるテロメラーゼ活性の発現に関する研究

 

研究分野 【 表示 / 非表示

  • 生理学一般

  • 整形外科学

研究キーワード 【 表示 / 非表示

  • 筋代謝

  • 骨代謝

  • 軟骨代謝

  • 運動器学

 

論文 【 表示 / 非表示

  • Innervation of the tibial epiphysis through the intercondylar foramen

    Matsuo K., Ji S., Miya A., Yoda M., Hamada Y., Tanaka T., Takao-Kawabata R., Kawaai K., Kuroda Y., Shibata S.

    Bone (Elsevier)  120   297 - 304 2019年03月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  87563282

     概要を見る

    The periosteum and mineralized bone are innervated by nerves that sense pain. These include both myelinated and unmyelinated neurons with either free nerve endings or bearing nociceptors. Parasympathetic and sympathetic autonomic nerves also innervate bone. However, little is known about the route sensory nerves take leaving the epiphyses of long bones at the adult knee joint. Here, we used transgenic mice that express fluorescent Venus protein in Schwann cells (Sox10-Venus mice) to visualize myelinated and unmyelinated nerves in the tibial epiphysis. Immunofluorescence to detect a pan-neuronal marker and the sensory neuron markers calcitonin gene-related peptide (CGRP) and tropomyosin receptor kinase A (TrkA) also revealed Schwann cell-associated sensory neurons. Foramina in the intercondylar area of the tibia were conserved between rodents and primates. Venus-labeled fibers were detected within bone marrow of the proximal epiphysis, exited through foramina along with blood vessels in the intercondylar area of the tibia, and joined Venus-labeled fibers of the synovial membrane and meniscus. These data suggest that innervation of the subchondral plate and trabecular bone within the tibial epiphysis carries pain signals from the knee joint to the brain through intercondylar foramina.

  • Trans-pairing between osteoclasts and osteoblasts shapes the cranial base during development

    Edamoto M., Kuroda Y., Yoda M., Kawaai K., Matsuo K.

    Scientific Reports (Springer Nature)  9 ( 1 )  2019年02月

    研究論文(学術雑誌), 共著, 査読有り

     概要を見る

    Bone growth is linked to expansion of nearby organs, as is the case for the cranial base and the brain. Here, we focused on development of the mouse clivus, a sloping surface of the basioccipital bone, to define mechanisms underlying morphological changes in bone in response to brain enlargement. Histological analysis indicated that both endocranial and ectocranial cortical bone layers in the basioccipital carry the osteoclast surface dorsally and the osteoblast surface ventrally. Finite element analysis of mechanical stress on the clivus revealed that compressive and tensile stresses appeared mainly on respective dorsal and ventral surfaces of the basioccipital bone. Osteoclastic bone resorption occurred primarily in the compression area, whereas areas of bone formation largely coincided with the tension area. These data collectively suggest that compressive and tensile stresses govern respective localization of osteoclasts and osteoblasts. Developmental analysis of the basioccipital bone revealed the clivus to be angled in early postnatal wild-type mice, whereas its slope was less prominent in Tnfsf11 −/− mice, which lack osteoclasts. We propose that osteoclast-osteoblast “trans-pairing” across cortical bone is primarily induced by mechanical stress from growing organs and regulates shape and size of bones that encase the brain.

  • Granulocyte-colony stimulating factor enhances load-induced muscle hypertrophy in mice

    Ohashi M., Okubo K., Mizuno S., Yoda M., Shirasawa H., Chiba K., Horiuchi K., Matsumoto M., Nakamura M.

    Biochemical and Biophysical Research Communications (Elsevier)  506 ( 4 ) 944 - 949 2018年12月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  0006291X

     概要を見る

    Granulocyte-colony stimulating factor (G-CSF) is a cytokine crucially involved in the regulation of granulopoiesis and the mobilization of hematopoietic stem cells from bone marrow. However, emerging data suggest that G-CSF exhibits more diverse functions than initially expected, such as conferring protection against apoptosis to neural cells and stimulating mitogenesis in cardiomyocytes and skeletal muscle stem cells after injury. In the present study, we sought to investigate the potential contribution of G-CSF to the regulation of muscle volume. We found that the administration of G-CSF significantly enhances muscle hypertrophy in two different muscle overload models. Interestingly, there was a significant increase in the transcripts of both G-CSF and G-CSF receptors in the muscles that were under overload stress. Using mutant mice lacking the G-CSF receptor, we confirmed that the anabolic effect is dependent on the G-CSF receptor signaling. Furthermore, we found that G-CSF increases the diameter of myotubes in vitro and induces the phosphorylation of AKT, mTOR, and ERK1/2 in the myoblast-like cell line C2C12 after differentiation induction. These findings indicate that G-CSF is involved in load-induced muscle hypertrophy and suggest that G-CSF is a potential agent for treating patients with muscle loss and sarcopenia.

  • Targeted ablation of p38α MAPK suppresses denervation-induced muscle atrophy

    Yuasa Kazuki, Okubo Kazumasa, Yoda Masaki, Otsu Kinya, Ishii Yasuyuki, Nakamura Masaya, Itoh Yoshiki, Horiuchi Keisuke

    Scientific Reports (Springer Nature)  8 ( 1 )  2018年12月

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  2045-2322

     概要を見る

    The loss of skeletal muscle mass is a major cause of falls and fractures in the elderly, leading to compromised independence and a decrease in the quality of life. However, only a few therapeutic interventions leading to marginal clinical benefits in patients with this condition are currently available. Therefore, the demand to further understand the pathology of muscle atrophy and establish a treatment modality for patients with muscle atrophy is significant. p38α mitogen-activated protein kinase (p38α MAPK) is a ubiquitous signaling molecule that is implicated in various cellular functions, including cell proliferation, differentiation, and senescence. In the present study, we generated a mutant line in which p38α MAPK is specifically abrogated in muscle tissues. Compared with the control mice, these mutant mice are significantly resistant to denervation-induced muscle atrophy, suggesting that p38α MAPK positively regulates muscle atrophy. We also identified CAMK2B as a potential downstream target of p38α MAPK and found that the pharmacological inhibition of CAMK2B activity suppresses denervation-induced muscle atrophy. Altogether, our findings identify p38α MAPK as a novel regulator of muscle atrophy and suggest that the suppression of intracellular signaling mediated by p38α MAPK serves as a potential target for the treatment of muscle atrophy.

  • Inhibition of ADAM10 in satellite cells accelerates muscle regeneration following muscle injury

    Mizuno S, Yoda M, Shimoda M, Chiba K, Nakamura M, Horiuchi K

    Journal of Orthopaedic Research (Wiley)  36 ( 8 ) 2259 - 2265 2018年

    研究論文(学術雑誌), 共著, 査読有り,  ISSN  07360266

     概要を見る

    Muscle injury is one of the most common orthopedic and sports disorders. For severe cases, surgical repair may be indicated; however, other than immobilization and the administration of anti-inflammatory drugs there is currently no effective conservative treatment for this condition. Satellite cells (SCs) are muscle-specific stem cells and are indispensable for muscle regeneration after muscle injury. SCs are activated upon muscle injury to proliferate and differentiate into myoblasts, which subsequently fuse into myofibers and regenerate the damaged muscle. We have previously shown that ADAM10, a membrane-anchored proteolytic enzyme, is essential for the maintenance of SC quiescence by activating the Notch signaling pathway in SCs. Because suppression of ADAM10 activity in SCs can activate SC differentiation, we asked whether inactivation of ADAM10 in SCs after muscle injury could enhance muscle regeneration. Using Adam10 conditional knockout mice, in which ADAM10 activity can specifically be suppressed in SCs, we found that partial inactivation of ADAM10 accelerates muscle regeneration after muscle injury. Nearly identical results were obtained by the administration of GI254023X, a selective ADAM10 inhibitor. The findings of the present study thus indicate that transient enhancement of SC differentiation after muscle injury expedites muscle regeneration and that ADAM10 can be a potential molecular target in treating muscle injuries.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

研究発表 【 表示 / 非表示

  • マウス腓骨における骨形成部位は成長に伴い変位する

    依田 昌樹、黒田 有希子、松尾 光一

    第36回日本骨代謝学会学術集会 (長崎、日本) , 2018年07月, ポスター(一般)

  • Bone Renovation of the Mouse Neonatal Fibula into the Adult Skeleton

    Yoda Masaki, Kuroda Yukiko, Matsuo, Koichi

    America Society for Bone and Mineral Research 2017 Annual Meeting (Denver, CO, USA) , 2017年09月, ポスター(一般)

  • マウス腓骨における内軟骨性骨化後の断面形状の改変

    依田 昌樹、黒田 有希子、松尾 光一

    第35回日本骨代謝学会学術集会 (福岡、日本) , 2017年07月, 口頭(一般)

  • 軟骨細胞におけるADAM10-Notchシグナルの抑制は顕著な成長障害を来たす

    依田昌樹、水野早季子、秋山治彦、戸山芳昭、松本守雄、堀内圭輔

    第28回日本軟骨代謝学会 (東京、日本) , 2015年03月, 口頭(一般)

  • 軟骨細胞特異的なADAM10-Notchシグナルの抑制は顕著な成長障害を来たす

    依田昌樹、水野早季子、秋山治彦、松本守雄、戸山芳昭、堀内圭輔

    第32回日本骨代謝学会学術集会 (大阪、日本) , 2014年07月, ポスター(一般)

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競争的資金等の研究課題 【 表示 / 非表示

  • 3次元濃度勾配を有する細胞培養実現のための徐放性磁気ビーズの開発

    2017年10月
    -
    2018年09月

    JSR株式会社, 学術開発プロジェクト, 依田 昌樹, 代表

  • 軟骨原基を形成する形態形成関連因子の三次元的解析

    2017年04月
    -
    2020年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 依田 昌樹, 基盤研究(C), 代表

  • ADAM10を介した骨・軟骨形成の制御機構

    2014年04月
    -
    2017年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 依田 昌樹, 基盤研究(C), 代表

     研究概要を見る

    本研究では膜型メタロプロテアーゼADAM10による骨・軟骨形成および破骨細胞分化の制御機構を明らかにすることを目的とした.軟骨特異的にADAM10を欠損させたマウスの解析から,軟骨細胞の最終分化にADAM10は必須であることが明らかとなった.また,骨芽細胞特異的にADAM10を欠損させたマウスの解析から,ADAM10を骨芽細胞で欠損させると血液中のTSLP濃度が上昇し重篤な皮膚炎を発症することが明らかとなった.さらに,ADAM10を欠損させた破骨細胞前駆細胞を用いた分化誘導実験から,ADAM10の基質であるNotchレセプターからのシグナルが破骨細胞分化を完全に抑制することが明らかとなった.

  • 筋・骨格形成および造血におけるシェディングの機能解析

    2012年04月
    -
    2016年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 堀内 圭輔, 基盤研究(B), 分担

     研究概要を見る

    本研究では膜型タンパク質分解酵素ADAM17およびADAM10の機能を多岐にわたって解析を行った.本研究結果から,1)ADAM17が成長軟骨の吸収を制御していること,2)ADAM17はIL-1のⅡ型受容体を特異的に切断し,IL-1シグナルを正に制御しうること,また3)ADAM17その活性が転写・翻訳レベルでの制御をほとんど受けないことを明らかにした.一方,ADAM10に関しては,筋衛星細胞の恒常性維持に必須であることを解明した.またこれらの研究と並行し,破骨細胞における小胞体ストレスの機能を解析し,小胞体ストレスセンサーIRE1αを介し破骨細胞分化を制御することを明らかにした。

  • Notchシグナリングが関与する骨代謝調節機構の解明

    2012年04月
    -
    2013年03月

    中冨健康科学振興財団, 研究助成事業, 依田 昌樹, 研究助成金, 代表

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受賞 【 表示 / 非表示

  • 優秀ポスター賞

    2014年07月, 日本骨代謝学会, 軟骨細胞特異的なADAM10-Notchシグナルの抑制は 顕著な成長障害を来たす

    受賞区分: 国内学会・会議・シンポジウム等の賞,  受賞国: 日本

  • Young Investigator Award

    2005年06月, 国際粘膜免疫学会

    受賞区分: 国際学会・会議・シンポジウム等の賞,  受賞国: アメリカ