Kuroda, Yukiko



School of Medicine, Center for Integrated Medical Research (Shinanomachi)



External Links

Career 【 Display / hide

  • 2007.04

    独立行政法人理化学研究所, 脳科学総合センター 発生神経生物研究チーム, 研究員

  • 2008.04

    独立行政法人理化学研究所, 脳科学総合センター 発生神経生物研究チーム, 基礎科学特別研究員

  • 2011.04

    慶應義塾大学医学部, 共同利用研究室・細胞組織学研究室, 特任助教

  • 2014.04

    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

Academic Background 【 Display / hide

  • 1996.04

    Tohoku University, 農学部, 応用生物化学科

    University, Graduated

  • 2000.04

    Tohoku University, 農学部, 農学研究科応用生命科学専攻

    Graduate School, Completed, Master's course

  • 2003.04

    The University of Tokyo, 医学部, 医学系研究科脳神経医学専攻

    Graduate School, Completed, Doctoral course


Research Areas 【 Display / hide

  • Life Science / Morphology and anatomical structure

  • Life Science / Clinical pharmacy

  • Life Science / Physiology

  • Life Science / Anatomy

Research Keywords 【 Display / hide

  • Morphology

  • Mineralization

  • cellular interaction

  • bone


Papers 【 Display / hide

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

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

    Scientific reports (Scientific Reports)  9 ( 1 ) 1956 2019.12

    Joint Work, Accepted

     View Summary

    © 2019, The Author(s). 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.

  • 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 (Bone)  120   297 - 304 2019.03

    Joint Work, Accepted,  ISSN  87563282

     View Summary

    © 2018 The Authors 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.

  • Effects of long-term cigarette smoke exposure on bone metabolism, structure, and quality in a mouse model of emphysema

    Sasaki Mamoru, Chubachi Shotaro, Kameyama Naofumi, Sato Minako, Haraguchi Mizuha, Miyazaki Masaki, Takahashi Saeko, Nakano Takayoshi, Kuroda Yukiko, Betsuyaku Tomoko, Matsuo Koichi

    PLoS One (PLoS ONE)  13 ( 1 ) e0191611 2018.01

    Research paper (scientific journal), Joint Work,  ISSN  1932-6203

     View Summary

    <p>Smoking is a common risk factor for both chronic obstructive pulmonary disease (COPD) and osteoporosis. In patients with COPD, severe emphysema is a risk factor for vertebral fracture; however, the effects of smoking or emphysema on bone health remain largely unknown. We report bone deterioration in a mouse model of emphysema induced by nose-only cigarette smoke (CS) exposure. Unexpectedly, short-term exposure for 4-weeks decreased bone turnover and increased bone volume in mice. However, prolonged exposure for 20- and 40-weeks reversed the effects from suppression to promotion of bone resorption. This long-term CS exposure increased osteoclast number and impaired bone growth, while it increased bone volume. Strikingly, long-term CS exposure deteriorated bone quality of the lumbar vertebrae as illustrated by disorientation of collagen fibers and the biological apatite c-axis. This animal model may provide a better understanding of the mechanisms underlying the deterioration of bone quality in pulmonary emphysema caused by smoking.</p>

  • Dissection of the auditory bulla in postnatal mice

    Sakamoto Ayako, Kuroda Yukiko, Kanzaki Sho, Matsuo Koichi

    Journal of Visualized Experiments (Journal of Visualized Experiments)  2017 ( 119 )  2017.01

    Research paper (scientific journal), Joint Work,  ISSN  1940-087X

     View Summary

    <p>In most mammals, auditory ossicles in the middle ear, including the malleus, incus and stapes, are the smallest bones. In mice, a bony structure called the auditory bulla houses the ossicles, whereas the auditory capsule encloses the inner ear, namely the cochlea and semicircular canals. Murine ossicles are essential for hearing and thus of great interest to researchers in the field of otolaryngology, but their metabolism, development, and evolution are highly relevant to other fields. Altered bone metabolism can affect hearing function in adult mice, and various gene-deficient mice show changes in morphogenesis of auditory ossicles in utero. Although murine auditory ossicles are tiny, their manipulation is feasible if one understands their anatomical orientation and 3D structure. Here, we describe how to dissect the auditory bulla and capsule of postnatal mice and then isolate individual ossicles by removing part of the bulla. We also discuss how to embed the bulla and capsule in different orientations to generate paraffin or frozen sections suitable for preparation of longitudinal, horizontal, or frontal sections of the malleus. Finally, we enumerate anatomical differences between mouse and human auditory ossicles. These methods would be useful in analyzing pathological, developmental and evolutionary aspects of auditory ossicles and the middle ear in mice.</p>

  • Osteoprotegerin regulates pancreatic β-cell homeostasis upon microbial invasion

    Kuroda Yukiko, Maruyama Kenta, Fujii Hideki, Sugawara Isamu, Ko Shigeru B H, Yasuda Hisataka, Matsui Hidenori, Matsuo Koichi

    PLoS One (PUBLIC LIBRARY SCIENCE)  11 ( 1 ) e0146544 2016.01

    Research paper (scientific journal), Joint Work,  ISSN  1932-6203

     View Summary

    <p>Osteoprotegerin (OPG), a decoy receptor for receptor activator of NF-κB ligand (RANKL), antagonizes RANKL's osteoclastogenic function in bone. We previously demonstrated that systemic administration of lipopolysaccharide (LPS) to mice elevates OPG levels and reduces RANKL levels in peripheral blood. Here, we show that mice infected with Salmonella, Staphylococcus, Mycobacteria or influenza virus also show elevated serum OPG levels. We then asked whether OPG upregulation following microbial invasion had an effect outside of bone. To do so, we treated mice with LPS and observed OPG production in pancreas, especially in β-cells of pancreatic islets. Insulin release following LPS administration was enhanced in mice lacking OPG, suggesting that OPG inhibits insulin secretion under acute inflammatory conditions. Consistently, treatment of MIN6 pancreatic β-cells with OPG decreased their insulin secretion following glucose stimulation in the presence of LPS. Finally, our findings suggest that LPS-induced OPG upregulation is mediated in part by activator protein (AP)-1 family transcription factors, particularly Fos proteins. Overall, we report that acute microbial infection elevates serum OPG, which maintains β-cell homeostasis by restricting glucose-stimulated insulin secretion, possibly preventing microbe-induced exhaustion of β-cell secretory capacity.</p>

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

Reviews, Commentaries, etc. 【 Display / hide

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Presentations 【 Display / hide

  • Hypermineralizing osteoblasts produce type II collagen-containing high BMD bone

    Yukiko Kuroda

    The 37th Annual Meeting of the Japanese Society for Bone and Mineral Research (神戸国際会議場) , 


    Oral presentation (general), Japanese Society for Bone and Mineral Research

  • Hypermineralization of bones by Col2a1-expressing osteoblasts

    Kuroda Yukiko

    ASBMR 2018 Annual meeting (Palais des congres de Montreal, Montreal, Quebec, Canada) , 


    Oral presentation (general)

  • High BMD bones are built by Col2a1-expressing“hypermineralizing osteoblasts”

    Kuroda Yukiko

    第36回日本骨代謝学会学術集会 (長崎ブリックホール) , 


    Oral presentation (general)

  • A novel osteoblast subpopulation initiates endochondral ossification by forming osteogenic capillaries

    Kuroda Yukiko

    ASBMR 2017 Annual Meeting, 


    Poster presentation

  • Col1a1low骨芽細胞は内軟骨性骨化で働く新たな骨芽細胞群である

    Kuroda Yukiko



    Oral presentation (general)

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

  • 感覚器における骨組織の役割~聴覚器に特化した骨形態・骨代謝制御機構の解明


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

  • 高い骨密度の骨を形成する新規骨芽細胞群「超石灰化骨芽細胞」の解析


    Keio University, Grant-in-Aid for Scientific Research (C), No Setting

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  • Osteogenic capillaries - new aspect of endochondral ossification


    Keio University, Grant-in-Aid for Scientific Research (B), No Setting

     View Summary

    1. 内軟骨性骨化によって骨になる耳小骨や長管骨の解析から、内軟骨性骨化過程で働く新たな「内軟骨性骨芽細胞」の実体を明らかにしようと実験を進めた。その結果、耳小骨で見出された「内軟骨性骨芽細胞」と類似した細胞が、(成長板直下の軟骨・骨移行部ではなく)上腕骨遠位部の骨膜下などの、骨密度が特別に高い部分に存在することがわかった。意義:研究対象の細胞を、予測される機能に基づき「超石灰化骨芽細胞(hypermineralizing osteoblasts)」と呼ぶこととし、実体の解明が進んだ。
    推進方策1.超石灰化骨芽細胞と骨密度の高い骨(の部分)との関係を明らかにする。Col1(Low)Col2(High)骨芽細胞を、超石灰化骨芽細胞(Hypermineralizing osteoblasts)として一般化できるかどうかを検討する。

  • 骨吸収窩糖タンパク質が誘導する新規骨形成制御機構の解明


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

  • Identification of bone formation mechanisms at resorption lacunae


    Keio University, Kuroda Yukiko, Grant-in-Aid for Scientific Research (C), No Setting

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    Abundant glycoproteins exist in bone resorption pits, whereas their physiological roles remain unknown. In this study, I observed that glycoproteins sticking to the surface of resorption pits were produced by mature osteoclasts, but not osteoclast precursors. I also found a novel lectin that tightly bound to a bone reporption pit by lectin microarray analysis, and this lectin specifically recognized osteoclasts and blood vessels in vivo. Matrix metalloproteinase was identified as a major protein that bound to the lectin in those mature osteoclast secreted. Finally, the osteoblast culture experiment suggested the possibility that bone resorption pits could modulate osteoblast migration.

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Awards 【 Display / hide

  • L'ORÉAL-UNESCO For Women in Science Japan Fellowships



Courses Taught 【 Display / hide











Courses Previously Taught 【 Display / hide

  • メディカル・プロフェッショナリズム III

    Keio University


    Spring Semester, Lecture, Lecturer outside of Keio


  • メディカル・プロフェッショナリズム III

    Keio University


    Spring Semester, Lecture, Lecturer outside of Keio



Memberships in Academic Societies 【 Display / hide

  • 日本骨代謝学会

  • American Society for Bone and Mineral Research