Kuroda, Yukiko

写真a

Affiliation

School of Medicine, Collaborative Research Resources (Laboratory of Cell and Tissue Biology) (Shinanomachi)

Position

Instructor

External Links

Career 【 Display / hide

  • 2007.04
    -
    2008.03

    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
    -
    2011.03

    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
    -
    2014.03

    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
    -
    Present

    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
    -
    2000.03

    Tohoku University, 農学部, 応用生物化学科

    University, Graduated

  • 2000.04
    -
    2002.03

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

    日本, Graduate School, Completed, Master's course

  • 2003.04
    -
    2007.03

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

    日本, Graduate School, Completed, Doctoral course

 

Research Areas 【 Display / hide

  • Morphology/Structure

  • General physiology

  • General anatomy (including histology/embryology)

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

    Joint Work, Except for reviews,  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

    Joint Work, Except for reviews,  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 (PLoS ONE)  11 ( 1 ) e0146544 2016.01

    Joint Work, Except for reviews

     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

Presentations 【 Display / hide

  • Hypermineralization of bones by Col2a1-expressing osteoblasts

    Kuroda Yukiko

    ASBMR 2018 Annual meeting (Palais des congres de Montreal, Montreal, Quebec, Canada) , 2018.09, 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) , 2018.07, Oral Presentation(general)

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

    Kuroda Yukiko

    ASBMR 2017 Annual Meeting, 2017.09, Poster (general)

  • 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

    第35回日本骨代謝学会学術集会, 2017.07, Oral Presentation(general)

  • 内軟骨性骨化~軟骨が骨に置き換わる部位では特殊な骨芽細胞が働いていた

    Kuroda Yukiko

    第16回松本ボーンフォーラム (信州大学医学部附属病院新外来棟4階 大会議室) , 2017.05, Oral Presentation(general)

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

  • 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

    2019.04
    -
    2022.03

    Keio University, 黒田 有希子, Grant-in-Aid for Scientific Research (C)

  • Osteogenic capillaries - new aspect of endochondral ossification

    2017.04
    -
    2021.03

    Keio University, 松尾 光一, 黒田 有希子, Grant-in-Aid for Scientific Research (B)

     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。
    2.I型コラーゲンの発現細胞を可視化できるCol1a1-GFPマウスを用いた解析から、耳小骨の「超石灰化骨芽細胞」はI型コラーゲンの発現が低く、II型コラーゲンの発現が高いことが分かった。骨芽細胞マーカーであるオステオカルシンに陽性、Col1a1-GFPマウスでGFP陰性、かつ骨標識剤アリザリンでラベルされる骨形成部位に局在するという指標を用いて同定できることがわかった。意義:本来骨基質のタンパク質の9割程度を占めるI型コラーゲンだけでなく、軟骨に含まれるII型コラーゲンも産生する骨芽細胞が存在することが初めて明らかになった。
    3.放射光施設SPring-8におけるX線位相顕微鏡を用いたマイクロCT解析により、腓骨における通常の骨芽細胞と、耳小骨における「超石灰化骨芽細胞」の両方を、細胞レベルで可視化できた。意義:内軟骨性骨化の過程を細胞レベルで空間的に把握することができるようになった。骨芽細胞と毛細血管の空間的な位置関係の情報が得られた。
    4.耳小骨以外のマウスの骨格全体で、「超石灰化骨芽細胞」の主な存在部位が明らかになった。
    「長管骨の成長板直下の軟骨・骨移行部では、通常の骨芽細胞とは異なる「内軟骨性骨芽細胞」が、骨形成性毛細血管を構成して、軟骨基質上に骨基質を添加する」という当初の作業仮説を追究した結果、耳小骨で内軟骨性骨化を担う骨芽細胞に似た骨芽細胞が、マウス骨格の成長板以外の部位に見出された。これは予期しない知見であったものの、新たに見出された「超石灰化骨芽細胞」が耳小骨の骨化に限られた特殊なものではなく、石灰化度の高い様々な部位に存在する普遍的な骨芽細胞である可能性が示され、「超石灰化骨芽細胞」が通常の骨芽細胞とは異なることが明確になってきたから。
    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。
    2.超石灰化骨芽細胞の分化条件を検討する。骨軟骨前駆細胞株を用いて、細胞外マトリックスの組成や成長因子の添加などを変えて、試験管内で超石灰化骨芽細胞が出現する条件を解明する。
    3.超石灰化骨芽細胞と骨形成性毛細血管の関係の解析。耳小骨では、毛細血管周囲に骨芽細胞が配列していたが、耳小骨以外の部位での超石灰化骨芽細胞が毛細血管に直接的に接触しているかどうかは知られていない。免疫組織化学などを駆使して、血管内皮細胞と超石灰化骨芽細胞との関係を解明する。

  • 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

    2016.04
    -
    2019.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 黒田 有希子, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • Identification of bone formation mechanisms at resorption lacunae

    2013.04
    -
    2016.03

    Keio University, Kuroda Yukiko, Grant-in-Aid for Scientific Research (C)

     View Summary

    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.

  • The investigation and identification of key molecules in the calciumoscillation-independent osteoclastogenesis

    2011
    -
    2012

    Keio University, KURODA Yukiko, Grant-in-Aid for Young Scientists (B)

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    In this study, I found that direct contact between osteoclasts and osteoblasts,especially membrane fraction molecule(s) of osteoblasts, is required for the inductionof Ca^<2+>oscillation-independent osteoclastogenesis. Moreover, I revealed that Cot, aseri

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Awards 【 Display / hide

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

    2007.07

 

Courses Taught 【 Display / hide

  • MEDICAL PROFESSIONALISM 3

    2019

Courses Previously Taught 【 Display / hide

  • メディカル・プロフェッショナリズム III

    Keio University, 2018, Spring Semester, General education subject, Lecture, Lecturer outside of Keio

    研究倫理

  • メディカル・プロフェッショナリズム III

    Keio University, 2017, Spring Semester, General education subject, Lecture, Lecturer outside of Keio

    研究倫理