松尾 光一 ( マツオ コウイチ )

Matsuo, Koichi

写真a

所属(所属キャンパス)

医学部 ( 三田 )

職名

名誉教授

HP

外部リンク

総合紹介 【 表示 / 非表示

  • 細胞組織学研究室のメンバー(2017)

    研究室は、破骨細胞、さらに破骨細胞と骨芽細胞の相互作用(カップリング)に関する一連の骨代謝学の研究で成果を挙げた。近年では、骨の三次元的な形態形成に研究の焦点を移し、内軟骨性骨化や生後の骨形態変化のメカニズムを、マウスやニホンザルなどの実験動物を用いて解析している。「多様なサイズとかたち」を生み出し、それを成長させ、維持し修復する細胞レベルのメカニズムは本質的なものであるにもかかわらず、不明な点が多い。新たな研究領域を開拓しようと、長管骨や椎骨に加え、耳小骨や頭蓋底骨などを対象として解析力を高めている。さらに放射光施設SPring-8(兵庫)におけるX線位相顕微鏡によるCT撮影(東北大学との共同研究)では、 細胞レベルの解像度で、内軟骨性骨化を担う骨形成性毛細血管の構造を明らかにした。研究室を挙げて形態形成原理の追究に精力を注いでいる。

経歴 【 表示 / 非表示

  • 2001年04月
    -
    2002年03月

    国立長寿医療研究センター老年病研究部, 室長

  • 2002年04月
    -
    2007年03月

    慶應義塾大学医学部, 微生物学・免疫学教室, 助教授

  • 2007年04月
    -
    2009年05月

    慶應義塾大学, 微生物学・免疫学教室, 准教授

  • 2009年06月
    -
    継続中

    慶應義塾大学医学部, 共同利用研究室(細胞組織学), 教授

  • 2009年10月
    -
    継続中

    総合医科学研究センター長

学位 【 表示 / 非表示

  • 博士(医学), 慶應義塾大学, 課程, 1992年09月

免許・資格 【 表示 / 非表示

  • 医師免許証, 1986年06月

 

研究分野 【 表示 / 非表示

  • 骨代謝学

  • 骨免疫学

  • ライフサイエンス / 細胞生物学 (Cell Biology)

  • ライフサイエンス / 解剖学 (General Anatomy(includes Histology/Embryology))

研究キーワード 【 表示 / 非表示

  • 破骨細胞

  • 耳小骨

  • 骨モデリング

  • 骨リモデリング

  • 骨細胞

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研究テーマ 【 表示 / 非表示

  • 内軟骨性骨化における骨形成性血管の解析, 

    2015年04月
    -
    継続中

  • 骨の形態形成とバイオミネラリゼーション・恒常性維持のメカニズムを、細胞間相互作用によって解明することを目指している。, 

    2000年
    -
    継続中

 

論文 【 表示 / 非表示

  • Bipixel rotation method: An algorithm for chirality analysis of biological mesh network

    Kumaki K., Kawaai K., Noji S., Kuroda Y., Matsuo K.

    Journal of Structural Biology X 14 2026年12月

     概要を見る

    Vertebrates are bilateral organisms characterized by both symmetrical and asymmetrical structures. While skeletons are grossly symmetrical, microscopic biological networks within the bone—such as cortical canals containing vascular networks—often exhibit deviations from precise mirror-image symmetry. These deviations make it challenging to detect subtle chiral biases amidst random structural variations. We developed the “bipixel rotation method” to quantify the extent of these biases, thereby enabling the characterization of porcine femoral cortical canals. In this approach, binarized 2D images are rotated stepwise and skeletonized, followed by the quantification of vertically adjacent pixel pairs. We defined “center angle” as the rotation angle that yields the peak vertical bipixel count, and calculated “down-right bias” based on the asymmetry of the distribution of vertical bipixels around this center angle. After validating the method using alphabetical fonts and geometric wallpaper patterns, we applied the method to the cortical canal layers in porcine fibrolamellar bone visualized via nano-computed tomography (nano-CT). The method successfully detected potential chirality in the cortical canals, identifying up-right versus down-right biases, demonstrating its capability to capture even subtle structural chirality. These results suggest that the bipixel method is a versatile tool for chirality analysis of diverse biological mesh structures in the body.

  • Matrix Metalloproteinase-13 Is an Unfavorable Prognostic Factor in Chordoma by Digesting Growth Inhibitory Collagens

    Oishi Y., Kawaai K., Tamura R., Kuroda Y., Noji S., Toda M., Matsuo K.

    Cancer Medicine 15 ( 2 )  2026年02月

     概要を見る

    Objective: Chordomas are low-grade but invasive tumors with limited therapies. Some conventional chordomas exhibit cartilage-like extracellular matrix (ECM). This study examined the expression and clinical significance of collagenases in chordomas. Methods: Brachyury-positive primary chordoma tissues were analyzed by immunohistochemistry for matrix metalloproteinase (MMP)13, MMP9, and cathepsin K, and by immunofluorescence for MMP13 and MMP9. ECM phenotype was categorized using safranin-O staining, where safranin-O marks cartilage-like ECM. We compared MMP13 expression scores and progression-free survival (PFS) between safranin-O-negative and -positive groups. Collagenase gene expression and protein localization in JHC7 cells were analyzed by quantitative PCR and immunocytochemistry, respectively. Collagen digestion activity was evaluated using fluorescein isothiocyanate–labeled type II collagen (COL2) in the presence or absence of an MMP13-specific inhibitor. Cell growth was evaluated in the presence of type I collagen (COL1) or COL2. Results: Safranin-O negative chordomas had shorter PFS than safranin-O positive chordomas (p = 0.016). MMP13 was expressed in human chordoma tissues and JHC7 cells; the MMP13 expression score was higher in safranin-O-negative chordomas than in safranin-O-positive chordomas (p = 0.018). JHC7 cells digested COL2, and digestion was partially but significantly inhibited by an MMP13-specific inhibitor (p < 0.05). COL2 inhibited the growth of JHC7 cells more strongly than COL1 in a dose-dependent manner (p < 0.01). Conclusions: MMP13 may promote aggressive behavior in chordoma by degrading growth-inhibitory COL2-rich ECM. These data support MMP13 as a potential unfavorable prognostic marker and therapeutic target in chordoma.

  • Complete omission of exon 21 from Slc12a2 transcripts in mice results in hearing loss

    Mutai H., Kuroda Y., Noji S., Ichikawa S., Matsuo K., Tanaka S., Kataoka N., Fujioka M., Matsunaga T.

    Scientific Reports 15 ( 1 )  2025年12月

     概要を見る

    Hereditary hearing loss is highly heterogeneous. SLC12A2 is linked to autosomal dominant nonsyndromic hearing loss, DFNA78, with all the pathogenic variants affecting the exon 21. The gene encodes a cotransporter NKCC1 crucial for regulating intracellular osmotic pressure and producing endolymph in the cochlea. We generated two mouse strains with heterologous Slc12a2 variants in the splice site of the exon 21 (Em1: NM_009194.3:c.2912-2 A > G and Em2: c.2912-4_2913del). Slc12a2<sup>Em2/Em2</sup> mice with complete skip of the exon 21 showed reduced endolymph on postnatal day 1 (P1), reduced stria vascularis (StV) and no auditory brainstem responses at 4 weeks. Reduced StV size was considered to be due to rebalance osmotic pressure, and upregulation of Cldn9 revealed by RNA-seq was considered as tissue response to repair the gaps from reduced cell sizes in the Slc12a2<sup>Em2/Em2</sup> cochlea. Female Slc12a2<sup>Em2/+</sup> mice also exhibited mild elevation of ABR thresholds in several sound frequencies. Slc12a2<sup>Em1/Em1</sup> mice showed normal hearing, presumably due to sufficient cotransporter activity from the 9 bases shorter transcript by cryptic splicing. Minigene assays indicated that a single nucleotide difference between humans and mice at the 5’ end of the exon 21 affects exon 21 splicing. Slc12a2<sup>Em2</sup> mouse is proposed as a model for studying DFNA78 pathology.

  • Use of a new micropattern tape method to detect chirality shifts in differentiating C2C12 cells

    Weng Q., Osaka T., Onoe H., Yoshida K., Kuroda Y., Matsuo K., Kawaai K.

    Plos One 20 ( 12 December )  2025年12月

     概要を見る

    Chirality is an intrinsic property of cells manifested as left-right (LR) asymmetry in terms of cellular morphology and organization, which influences cell behavior, migration, and tissue development. Traditional in vitro methods used to study cell chirality often require complex fabrication methods, limiting their accessibility and reproducibility. Here, we present a novel micropattern tape method that facilitates fabrication of high-quality rectangular micropatterns useful for efficient, high-throughput analysis of cell chirality. Using this method, we characterized chirality of C2C12 myoblasts and MC3T3-E1 osteoblasts, which respectively exhibit clockwise (CW) and counterclockwise (CCW) chirality relative to the long axis of the rectangle. We used the method to analyze how cellular differentiation impacts chirality and observed striking reversal of C2C12 cell chirality upon bone morphogenic protein-2 (BMP2)-induced osteoblastic differentiation. These results demonstrate that our micropattern tape method can effectively detect dynamic change of cell chirality during differentiation.

  • Osteoclast visualization: Tartrate-resistant acid phosphatase activity staining using NewFuchsin compatible with non-aqueous mounting and tissue clearing

    Nakamura T., Kawaai K., Kuroda Y., Matsuo K.

    Methodsx 14 2025年06月

     概要を見る

    Tartrate-resistant acid phosphatase (TRAP) staining is widely used to stain osteoclasts in histological bone sections. The red dye formed by the conventional TRAP enzymatic reaction using naphthol AS-MX (or AS-BI) phosphate and fast red-violet (or garnet) chromogens is readily soluble in alcohol or xylene and requires air-drying prior to cover slipping or the use of an aqueous mounting medium. However, the use of an aqueous mounting medium makes it difficult to store stained specimens for a long time. In this modified method, a new fuchsin (NewFuchsin) was used as a chromogen, which enabled dehydration and clearing after staining and the use of a non-aqueous organic solvent-based mounting medium. Samples prepared using this modified TRAP activity staining method (NewFuchsin TRAP staining) have the following advantages over conventional TRAP staining: • The staining of sections provides a clear histological image and allows for long-term preservation. • The red dye formed by NewFuchsin TRAP staining can be detected not only in the bright field, but also in the fluorescent field. • Combined with tissue clearing using ethyl cinnamate, osteoclasts are observed using three-dimensional imaging.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

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総説・解説等 【 表示 / 非表示

  • 骨細胞ネットワークによるバイオミネラリゼーション

    松尾光一

    Clinical calcium 25 ( 10 ) 1461 - 1466 2015年10月

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア), 単著,  ISSN  0917-5857

     概要を見る

    <p>Osteocytes and their dendrites form a large network called the lacuno-canalicular system in mammalian bone. Osteocytes are believed to directly contribute to regulation of mineralization and demineralization in bone matrix, in addition to their indirect regulation of these processes through osteoblasts and osteoclasts. Not only can the location and shape of osteocyte lacunae and canaliculi be spatially visualized in isolated bone samples using synchrotron radiation technology, but differences in the degree of mineralization throughout the lacuno-canalicular system can be detected and quantified. Currently, comparable observation of the time course of these activities in vivo is technically challenging. This review provides an overview of non-dynamic quantitative analysis in the lacuno-canalicular system. Such analysis has the potential to become a methodological basis for investigating osteocyte-dependent direct regulation of mineralization in bone diseases. </p>

  • 骨細胞による骨融解に対するグルココルチコイドの影響

    松尾 光一

    Clinical calcium 24 ( 9 ) 1337 - 1342 2014年09月

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア), 単著,  ISSN  0917-5857

  • 骨免疫から見た老化制御

    松尾光一

    Clinical calcium 23 ( 1 ) 59 - 64 2013年01月

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア), 単著,  ISSN  0917-5857

     概要を見る

    <p>In bones, aging manifests itself as a shift towards production of myeloid cells in bone marrow, a condition associated with increased chronic inflammation by macrophages and decreased bone mass due to excess bone resorption by osteoclasts. An increase in the ratio of RANKL, a cytokine promoting osteoclast differentiation, to osteoprotegerin (OPG) , which acts as a decoy RANKL receptor, cannot explain the observed increase in osteoclast production, as serum OPG levels increase with age in humans, apparently to levels insufficient to counteract bone loss and prevent fracture. Age-related increases in osteoclastogenesis, decreases in lymphopoiesis, and inflammation including arthritis are likely best explained by a vicious cycle of myeloid skewing and inflammation occurring in bone marrow. These activities are due to aging of both hematopoietic stem cells themselves and the bone marrow microenvironment (niche cells) , which supports hematopoiesis. Impaired osteoblastogenesis and niche cell function are most likely pathologies emerging from increased oxidative stress, peroxisome proliferator-activated receptorγ (PPARγ) activity, and adipogenesis in the aging bone marrow. Currently, administration of either OPG or an anti-RANKL antibody has proved beneficial to prevent block bone dysfunction and osteoporosis in the elderly. However, anti-aging interventions targeting mesenchymal stem cell differentiation in the bone marrow may also help counteract inflammation and osteoclastic bone loss and enhance osteoblastic bone formation.</p>

  • Eph-ehrinファミリー分子群による骨代謝制御

    Matsuo K、, Otaki N

    Clinical calcium 22 ( 11 ) 1669 - 1675 2012年11月

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア), 共著,  ISSN  0917-5857

  • 骨細胞による骨融解:骨小腔体積の計測

    松尾光一

    Clinical calcium 22 ( 5 ) 677 - 683 2012年05月

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア),  ISSN  0917-5857

     概要を見る

    <p>Osteocytes are present in osteocytic lacunae in both cortical and trabecular bone, where they are interconnected by numerous dendrites in osteocytic canaliculi. In mammals, osteocytes are the most abundant bone cells, outnumbering osteoclasts and osteoblasts. Osteoclasts are the primary bone-resorbing cells ; however, the concept that osteocytes resorb bone by a process called osteocytic osteolysis has been postulated to explain dynamic calcium release from bone in conditions as diverse as parathyroid hormone (PTH) stimulation, hibernation, glucocorticoid stimulation, and lactation. Osteocytic osteolysis remains a controversial concept, mainly because it is difficult to demonstrate experimentally. Recently, novel functions of osteocytes in mineral metabolism and bone remodeling have been reported, and osteocytic osteolysis is being examined more closely experimentally. This review discusses published literature relevant to osteocytic osteolysis and compares 2D and 3D measurements of the volume of osteocytic lacunae, which serve as anatomical evidence for "periosteocytic osteolysis" .</p>

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研究発表 【 表示 / 非表示

  • Mammalian-type Brn-1/Pou3f3 with 'homopolymeric amino acids (HPAAs)' is essential for stress-induced bone metabolic changes in mice

    松尾 光一

    [国際会議]  Australian New Zealand Bone & Mineral Society Annual Scientific Meeting (Hobart, Tasmania) , 

    2015年11月

    ポスター発表

  • Sialylated Glycans of MMP-9 Marak Bone Resorption Lacunae.

    松尾 光一

    [国際会議]  Annual Meeting of the American Society for Bone and Mineral Research (Seattle, Washington, USA) , 

    2015年10月

    ポスター発表

  • Seasonality in Bone Mineralization of Auditory Ossicles and Long Bones in the Primate Macaca fuscata

    松尾 光一

    [国際会議]  Annual Meeting of the American Society for Bone and Mineral Research (Seattle, Washington, USA) , 

    2015年10月

    ポスター発表

  • Continuous Parathyroid Hormone Injection in Mouse Has Differential Effects on Osteoclast Activation in Primary and Secondary Spongiosa.

    松尾 光一

    [国際会議]  Annual Meeting of the American Society for Bone and Mineral Research (Seattle, Washington, USA) , 

    2015年10月

    ポスター発表

  • EphB/ephrin-B interactions regulate stromal cell fate determination and bone marrow support

    松尾 光一

    [国際会議]  Annual Meeting of the American Society for Bone and Mineral Research (Seattle, Washington, USA) , 

    2015年10月

    ポスター発表

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競争的研究費の研究課題 【 表示 / 非表示

  • ホモキラル要素による左右相称骨格の構築技法

    2021年09月
    -
    2023年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 松尾 光一, 学術変革領域研究(A), 補助金,  研究代表者

  • 左右対称性の骨格が形成される細胞機構の理解に向けて

    2021年04月
    -
    2025年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 松尾 光一, 基盤研究(B), 補助金,  研究代表者

  • 骨形成性毛細血管からみた内軟骨性骨化の新しい概念

    2017年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 松尾 光一, 基盤研究(B), 補助金,  研究代表者

受賞 【 表示 / 非表示

  • 日本骨代謝学会学術賞

    2014年07月, 日本骨代謝学会

  • 北里賞

    2003年06月, 慶應義塾大学医学部

  • Young Investigator Award

    1997年09月, American Society for Bone and Mineral Research

 

担当授業科目 【 表示 / 非表示

  • 解剖学

    2026年度

  • 微生物学

    2026年度

  • メディカル・プロフェッショナリズムⅢ

    2026年度

  • 分子細胞生物学

    2025年度

  • 微生物学

    2025年度

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担当経験のある授業科目 【 表示 / 非表示

  • 微生物学 (細菌学各論 1,2)

    慶應義塾

    2015年04月
    -
    2016年03月

    春学期, 講義

  • メディカル・プロフェッショナリズム III (研究倫理)

    慶應義塾

    2015年04月
    -
    2016年03月

    春学期, 講義

  • 基礎分子細胞生物学 II

    慶應義塾

    2015年04月
    -
    2016年03月

    春学期, 講義

  • 基礎分子細胞生物学 II

    慶應義塾

    2014年04月
    -
    2015年03月

    春学期, 講義

  • 微生物学 (細菌学各論 1,2)

    慶應義塾

    2014年04月
    -
    2015年03月

    春学期, 講義

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所属学協会 【 表示 / 非表示

  • 日本骨代謝学会

     
  • 米国骨代謝学会

     
  • 国際骨代謝学会