Kawaai, Katsuhiro



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



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Career 【 Display / hide

  • 2009.04

    科学技術振興機構, カルシウム振動プロジェクト, 研究員

  • 2011.04

    RIKEN, 研究員


Research Areas 【 Display / hide

  • Life Science / Molecular biology

  • Life Science / Neuroscience-general

  • Life Science / Biomaterials

Research Keywords 【 Display / hide

  • 包括脳ネットワーク


Books 【 Display / hide

  • 分子細胞生物学辞典, 第2版

    河合克宏, 東京化学同人, 2008.10

    Scope: 「4.1」「ドーパミントランスポーター」「Parkin」「Pax」「VEGF受容体」「スクランブラーマウス」「ヨタリマウス」「disabled homolog 1」「リーラーマウス」「小脳プルキンエ細胞欠失ミュータントマウス」「スタゲラーマウス」「ナーバスマウス」「pcdマウス」「シナプス後肥厚部」「バーグマングリア」

Papers 【 Display / hide

  • 中耳や内耳を構成する高石灰化骨を造る聴覚骨芽細胞の解析

    黒田 有希子, 河合 克宏, 石本 卓也, 中野 貴由, 百生 敦, 松尾 光一, 波多野 直哉, Wu Yanlin, 高野 秀和, Roschger Paul, Blouin Stephane

    日本骨代謝学会学術集会プログラム抄録集 ((一社)日本骨代謝学会)  39回   133 - 133 2021.10

    ISSN  1349-0761

  • Hypermineralization of hearing-related bones by a specific osteoblast subtype.

    Yukiko Kuroda, Katsuhiro Kawaai, Naoya Hatano, Yanlin Wu, Hidekazu Takano, Atsushi Momose, Takuya Ishimoto, Takayoshi Nakano, Paul Roschger, Stéphane Blouin, Koichi Matsuo

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 36 ( 8 ) 1535 - 1547 2021.04

    Accepted,  ISSN  0884-0431

     View Summary

    Auditory ossicles in the middle ear and bony labyrinth of the inner ear are highly mineralized in adult mammals. Cellular mechanisms underlying formation of dense bone during development are unknown. Here, we found that osteoblast-like cells synthesizing highly mineralized hearing-related bones produce both type I and type II collagens as the bone matrix, while conventional osteoblasts and chondrocytes primarily produce type I and type II collagens, respectively. Furthermore, these osteoblast-like cells were not labeled in a "conventional osteoblast"-specific green fluorescent protein (GFP) mouse line. Type II collagen-producing osteoblast-like cells were not chondrocytes as they express osteocalcin, localize along alizarin-labeled osteoid, and form osteocyte lacunae and canaliculi, as do conventional osteoblasts. Auditory ossicles and the bony labyrinth exhibit not only higher bone matrix mineralization but a higher degree of apatite orientation than do long bones. Therefore, we conclude that these type II collagen-producing hypermineralizing osteoblasts (termed here auditory osteoblasts) represent a new osteoblast subtype. This article is protected by copyright. All rights reserved.

  • Both IRBIT and long-IRBIT bind to and coordinately regulate Cl-/HCO3- exchanger AE2 activity through modulating the lysosomal degradation of AE2.

    Ryo Itoh, Naoya Hatano, Momoko Murakami, Kosuke Mitsumori, Satoko Kawasaki, Tomoka Wakagi, Yoshino Kanzaki, Hiroyuki Kojima, Katsuhiro Kawaai, Katsuhiko Mikoshiba, Koichi Hamada, Akihiro Mizutani

    Scientific reports 11 ( 1 ) 5990 - 5990 2021.03


     View Summary

    Anion exchanger 2 (AE2) plays crucial roles in regulating cell volume homeostasis and cell migration. We found that both IRBIT and Long-IRBIT (L-IRBIT) interact with anion exchanger 2 (AE2). The interaction occurred between the conserved AHCY-homologous domain of IRBIT/L-IRBIT and the N-terminal cytoplasmic region of AE2. Interestingly, AE2 activity was reduced in L-IRBIT KO cells, but not in IRBIT KO cells. Moreover, AE2 activity was slightly increased in IRBIT/L-IRBIT double KO cells. These changes in AE2 activity resulted from changes in the AE2 expression level of each mutant cell, and affected the regulatory volume increase and cell migration. The activity and expression level of AE2 in IRBIT/L-IRBIT double KO cells were downregulated if IRBIT, but not L-IRBIT, was expressed again in the cells, and the downregulation was cancelled by the co-expression of L-IRBIT. The mRNA levels of AE2 in each KO cell did not change, and the downregulation of AE2 in L-IRBIT KO cells was inhibited by bafilomycin A1. These results indicate that IRBIT binding facilitates the lysosomal degradation of AE2, which is inhibited by coexisting L-IRBIT, suggesting a novel regulatory mode of AE2 activity through the binding of two homologous proteins with opposing functions.

  • Transient appearance of Ca2+ -permeable AMPA receptors is crucial for the production of repetitive LTP-induced synaptic enhancement (RISE) in cultured hippocampal slices.

    Keiko Tominaga-Yoshino, Tomoyoshi Urakubo, Yukiko Ueno, Katsuhiro Kawaai, Shinichi Saito, Tomoko Tashiro, Akihiko Ogura

    Hippocampus 30 ( 7 ) 763 - 769 2020.04

    Joint Work, Accepted,  ISSN  1050-9631

     View Summary

    We have previously shown that repetitive induction of long-term potentiation (LTP) by glutamate (100 μM, 3 min, three times at 24-hr intervals) provoked long-lasting synaptic enhancement accompanied by synaptogenesis in rat hippocampal slice cultures, a phenomenon termed RISE (repetitive LTP-induced synaptic enhancement). Here, we examined the role of Ca2+ -permeable (CP) AMPA receptors (AMPARs) in the establishment of RISE. We first found a component sensitive to the Joro-spider toxin (JSTX), a blocker of CP-AMPARs, in a field EPSP recorded from CA3-CA1 synapses at 2-3 days after stimulation, but this component was not found for 9-10 days. We also observed that rectification of AMPAR-mediated current appeared only 2-3 days after stimulation, using a whole-cell patch clamp recording from CA1 pyramidal neurons. These findings indicate that CP-AMPAR is transiently expressed in the developing phase of RISE. The blockade of CP-AMPARs by JSTX for 24 hr at this developing phase inhibited RISE establishment, accompanied by the loss of small synapses at the ultrastructural level. These results suggest that transiently induced CP-AMPARs play a critical role in synaptogenesis in the developing phase of long-lasting hippocampal synaptic plasticity, RISE.

  • 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.

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

Reviews, Commentaries, etc. 【 Display / hide

  • IRBITは脂肪細胞分化初期の細胞増殖を制御している

    関口藍理, 浜田浩一, 佐藤聖子, 高橋透泰, 下田沙弥, 波多野直哉, 河合克宏, 御子柴克彦, 水谷顕洋

    聖マリアンナ医科大学雑誌(Web) (聖マリアンナ医科大学医学会)  44 ( 3 ) 183 (WEB ONLY) - 183 2016.11

    Other, Joint Work,  ISSN  2189-0285

  • IRBITはphosphatidylinositol phosphate kinasesの活性中心と結合する

    安東英明, 廣瀬松美, GAINCHE Laura, 河合克宏, BONNEAU Benjamin, 伊集院壮, 伊藤俊樹, 竹縄忠臣, 御子柴克彦

    日本生化学会大会(Web) 88th 2015

  • Genes associated with long-lasting synaptic enhancement in hippocampal slices after repetitive glutamate stimulation

    T. Tashiro, K. Kawaai, K. Tominaga-Yoshino, N. Taniguchi, H. Tashiro, A. Ogura


    ISSN  0022-3042

Presentations 【 Display / hide

  • Osteoclast differentiation factor induces osteolytic properties of chordoma

    河合克宏, 黒田有希子, 松尾光一



    Oral presentation (general)

  • Elucidation of the mechanisms for bone destruction in chordoma.

    Katsuhiro Kawaai, Yukiko Kuroda, Koichi Matsuo

    The 39rd Annual Meeting of the Japanese Society for Bone and Mineral Research, 


    Oral presentation (general)

  • 脊索腫における骨破壊機序の解明

    大石裕美子, 河合克宏, 田村亮太, 黒田有希子, 松尾光一, 戸田正博

    日本脳神経外科学会 第79回学術総会, 


  • 内軟骨性骨化における軟骨原基と骨の関係 -タルボX線位相トモグラフィー顕微鏡による形態解析-

    松尾光一, 姫シュウテイ, 黒田有希子, 河合克宏, 呉彦霖, 高野秀和, 百生敦



    Poster presentation

  • 内軟骨性骨化で形成される耳小骨は軟骨原基より小さい

    姫しゅうてい, 黒田有希子, 河合克宏, 百生 敦, 松尾光一



    Oral presentation (general)

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

  • Elucidation of the mechanisms for bone destruction in chordoma.


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

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  • Understanding the cellular basis of left-right symmetry in the skeleton


    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), No Setting

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    また、「トランスペアリング仮説」は、 “皮質骨を挟んだ破骨細胞と骨芽細胞の対合メカニズム(トランスペアリング)が存在して、成長過程で左右対称性の周囲組織の形態に応答し、骨が左右対称性に変容しながら成長する”というものである。2021年度は、組織学的解析を中心に、脛骨と腓骨などの長管骨におけるトランスペアリングの現象を組織学的手法、X線イメージング、蛍光イメージングで解析し、最初の論文の投稿を行った。現象論が中心だったので、さらにメカニズムを深めるための改訂作業を進める必要があるという認識に至った。
    「トランスペアリング」について:マウスの腓骨を中心に、骨芽細胞と破骨細胞の皮質骨を挟んだ分布を解析し、以前に報告した頭蓋底だけでなく(Edamoto et al, 2019, Sci Rep)、長管骨でも「トランスペアリング」が起こっているという現象を示すことができた。しかし、その具体的なメカニズムについては不明であり、2022年度以降に解明を目指す。
    フィブロネクチンのマイクロプリンティングの手法による、細胞培養レベルで右手型や左手型といった細胞のキラリティを検出する手法(Wan et al, 2011, PNAS)を、独自のアイデアで高度化し、スループットを上げて解析力を高める。具体的には、マイクロプリンティングのパターンをドーナツ型から直線の多い型にすること、PDMSスタンプにハンコのような持ち手を付けること、ステージ付きの電動ドリルの機構を利用して垂直にスタンプできるようにすることなどを検討する。

  • 骨化軟骨を模倣したバイオミメティクスコート材の開発および骨芽細胞動態解析による新規評価法の確立


    (株)JSR, 学術開発プロジェ クト (継続課題), Principal investigator

  • 骨化軟骨を模倣したバイオミメティクスコート材の開発および骨芽細胞動態解析による新規評価法の確立


    (株)JSR, 学術開発プロジェ クト (継続課題), Principal investigator

  • Applicational study of bone formation mechanism based on calcified cartilage


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

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    Based on the histological analysis of endochondral ossification, we found that calcified cartilage function as a superior scaffold for bone formation by osteoblasts. So, we performed screening of molecules enhance bone formation from components of calcified cartilage and applied to coating. We identified several candidate molecules and these coating on culture dish significantly enhanced in vitro bone formation by osteoblasts. In addition, we designed a surface micropattern inspired by characteristic structures of calcified cartilage. We also developed assay methods to evaluate the surface properties by using kinetics of osteoblast migration. The micropattern changed in vitro bone formation rate and cell migration speed of osteoblasts. From these examinations, we suggest that the combination of novel coating and surface micropatterns provide effective surface properties for implants to achieve high biological compatibility and secure engraftment.

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Courses Taught 【 Display / hide