YODA Masaki



School of Medicine, Department of Orthopaedic Surgery (Shinanomachi)


Project Assistant Professor (Non-tenured)/Project Research Associate (Non-tenured)/Project Instructor (Non-tenured)

External Links

Career 【 Display / hide

  • 2019.04

    慶應義塾大学, 医学部 整形外科学, 特任助教

  • 2016.04

    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

  • 2007.01

    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

Academic Background 【 Display / hide

  • 1997.04

    Tohoku University, 農学研究科, 資源生物科学専攻

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(農学), Tohoku University, Coursework, 2003.03



Research Areas 【 Display / hide

  • Life Science / Clinical pharmacy

  • Life Science / Physiology

  • Life Science / Orthopedics

Research Keywords 【 Display / hide

  • 筋代謝

  • 骨代謝

  • 軟骨代謝

  • 運動器学


Papers 【 Display / hide

  • ADAM17 protects against elastase-induced emphysema by suppressing CD62L<sup>+</sup> leukocyte infiltration in mice

    Suzuki S., Ishii M., Asakura T., Namkoong H., Okamori S., Yagi K., Kamata H., Kusumoto T., Kagawa S., Hegab A.E., Yoda M., Horiuchi K., Hasegawa N., Betsuyaku T.

    American journal of physiology. Lung cellular and molecular physiology (American journal of physiology. Lung cellular and molecular physiology)  318 ( 6 ) L1172 - L1182 2020.06

    Research paper (scientific journal), Accepted

     View Summary

    Pulmonary emphysema is a major manifestation of chronic obstructive pulmonary disease and is associated with chronic pulmonary inflammation caused by cigarette smoking, with contributions from immune cells such as neutrophils, macrophages, and lymphocytes. Although matrix metalloproteinases are well known to contribute to emphysema progression, the role of a disintegrin and metalloproteinase (ADAM) family proteins, other major metalloproteinases, in disease pathogenesis is largely unknown. ADAM17 is a major sheddase that cleaves various cell surface proteins, including CD62L, an adhesion molecule that plays a critical role in promoting the migration of immune cells to the site of inflammation. In the present study, we aimed to investigate the potential role of ADAM17 and CD62L in the development of elastase-induced emphysema. Control and Adam17flox/flox/Mx1-Cre (Adam17ΔMx1) mice (8-10 wk old) were intratracheally injected with 5 units of porcine pancreas elastase and monitored for 35 days after injection. Lung alveolar destruction was evaluated by analyzing the mean linear intercepts of lung tissue specimens and by histopathological examination. Mean linear intercepts data indicated that the degree of elastase-induced emphysema was significantly more severe in Adam17ΔMx1 mice. Furthermore, flow cytometry showed that CD62L+ neutrophil, CD62L+ macrophage, and CD62L+ B lymphocyte numbers were significantly increased in Adam17ΔMx1 mice. Moreover, the pharmacological depletion of CD62L+ cells with a CD62L-neutralizing antibody ameliorated the extent of emphysema in Adam17ΔMx1 mice. Collectively, these results suggest that ADAM17 possibly suppresses the progression of emphysema by proteolytically processing CD62L in immune cells and that ADAM17 and CD62L could be novel therapeutic targets for treating pulmonary emphysema.

  • ADAM10 is indispensable for longitudinal bone growth in mice

    Mizuno S., Yoda M., Kimura T., Shimoda M., Akiyama H., Chiba K., Nakamura M., Horiuchi K.

    Bone (Bone)  134 2020.05

    Research paper (scientific journal), Accepted,  ISSN  87563282

     View Summary

    © 2020 Skeletal development is a highly sophisticated process in which the expression of a variety of growth factors, signaling molecules, and extracellular matrix proteins is spatially and temporally orchestrated. In the present study, we show that ADAM10, a transmembrane protease that is critically involved in the functional regulation of various membrane-bound molecules, plays an essential role in the longitudinal growth of long bones and in skeletal development. We found that mutant mice lacking ADAM10 in osteochondroprogenitors exhibited marked growth retardation and had shorter long bones than the control mice. Histomorphometric analysis revealed that the mutant mice had a shorter hypertrophic zone and that their hypertrophic chondrocytes were smaller in size than those of the control mice. Unexpectedly, we found that the mRNA expression of the chemokine CXCL12 and its receptor CXCR4 were significantly reduced in cartilage tissues lacking ADAM10. Further, exogenous supplementation of recombinant CXCL12 rescued the defect in the ADAM10-deficient growth plate in an ex vivo culture model. Taken together, our data show a previously unknown role for ADAM10 in skeletal development that involves its regulation of the CXCL12 and CXCR4 signaling pathway.

  • 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 2019.03

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  87563282

     View Summary

    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 )  2019.02

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    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 2018.12

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0006291X

     View Summary

    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.

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Papers, etc., Registered in KOARA 【 Display / hide

Presentations 【 Display / hide

  • Bone formation site of mouse fibula transitions with growth

    Yoda Masaki, Kuroda Yukiko, Matsuo Koichi

    第36回日本骨代謝学会学術集会 (長崎、日本) , 


    Poster presentation

  • 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) , 


    Poster presentation

  • Reshaping of the mouse fibula after endochondral ossification

    Yoda Masaki, Kuroda Yukiko, Matsuo Koichi

    The 35th Annual Meeting of the Japanese Society for Bone and Mineral Research (Fukuoka, Japan) , 


    Oral presentation (general)

  • 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

    Abrogation of ADAM10 in chondrocytes results in severe dwarfism

    The 28th Annual Meeting of the Japanese Society of Cartilage Metabolism (Tokyo, Japan) , 


    Oral presentation (general)

  • 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


    第32回日本骨代謝学会学術集会 (Osaka, Japan) , 


    Poster presentation

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • Elucidation of the mechanism of skeletal muscle fibrosis associated with muscle injury and aging


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • 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


    JSR Corporation, Academic Development Project, Principal investigator

  • 軟骨原基を形成する形態形成関連因子の三次元的解析


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • Regulation of bone and cartilage formation by ADAM10


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

     View Summary

    In this study, we analyzed the regulation mechanisms of bone / cartilage formation and osteoclast differentiation by membrane type metalloprotease ADAM10. Analysis of mice abrogated ADAM10 in cartilage revealed that ADAM10 is essential for final differentiation of chondrocytes. In addition, analysis of osteoblast-specific ADAM10 deficient mice revealed that these mice indicated an increase in TSLP concentration in the serum and exhibited severe dermatitis. Furthermore, the experiment for osteoclast differentiation using osteoclast precursor lacking ADAM10 revealed that the signaling from Notch receptor, which is one of substrates for ADAM10, on the cell membrane of osteoclast precursor completely suppresses osteoclast differentiation.

  • 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


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Coinvestigator(s)

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Awards 【 Display / hide

  • 優秀ポスター賞

    2014.07, 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

    Type of Award: Award from Japanese society, conference, symposium, etc.

  • Young Investigator Award

    2005.06, Society for Mucosal Immunology

    Type of Award: Award from international society, conference, symposium, etc.,  Country: United States


Memberships in Academic Societies 【 Display / hide

  • 日本軟骨代謝学会, 

  • 日本分子生物学会, 

  • 日本骨代謝学会, 

  • 日本免疫学会,