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 共同利用研究室（細胞組織学研究室） （信濃町）

職名

教授（有期）

HP

外部リンク
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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。

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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

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学位 【 表示 ／ 非表示 】

  • 博士（医学）, 慶應義塾大学, 課程, 1992年09月

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免許・資格 【 表示 ／ 非表示 】

  • 医師免許証, 1986年06月

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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))

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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

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  • 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 ）  2019年12月

    　概要を見る

    © 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.

  • Parathyroid Hormone Shifts Cell Fate of a Leptin Receptor-Marked Stromal Population from Adipogenic to Osteoblastic Lineage

    Yang M., Arai A., Udagawa N., Zhao L., Nishida D., Murakami K., Hiraga T., Takao-Kawabata R., Matsuo K., Komori T., Kobayashi Y., Takahashi N., Isogai Y., Ishizuya T., Yamaguchi A., Mizoguchi T.

    Journal of Bone and Mineral Research （Journal of Bone and Mineral Research)  34 （ 10 ） 1952 - 1963 2019年10月

    ISSN  08840431

    　概要を見る

    © 2019 American Society for Bone and Mineral Research Intermittent parathyroid hormone (iPTH) treatment induces bone anabolic effects that result in the recovery of osteoporotic bone loss. Human PTH is usually given to osteoporotic patients because it induces osteoblastogenesis. However, the mechanism by which PTH stimulates the expansion of stromal cell populations and their maturation toward the osteoblastic cell lineage has not be elucidated. Mouse genetic lineage tracing revealed that iPTH treatment induced osteoblastic differentiation of bone marrow (BM) mesenchymal stem and progenitor cells (MSPCs), which carried the leptin receptor (LepR)-Cre. Although these findings suggested that part of the PTH-induced bone anabolic action is exerted because of osteoblastic commitment of MSPCs, little is known about the in vivo mechanistic details of these processes. Here, we showed that LepR+MSPCs differentiated into type I collagen (Col1)+ mature osteoblasts in response to iPTH treatment. Along with osteoblastogenesis, the number of Col1+ mature osteoblasts increased around the bone surface, although most of them were characterized as quiescent cells. However, the number of LepR-Cre-marked lineage cells in a proliferative state also increased in the vicinity of bone tissue after iPTH treatment. The expression levels of SP7/osterix (Osx) and Col1, which are markers for osteoblasts, were also increased in the LepR+MSPCs population in response to iPTH treatment. In contrast, the expression levels of Cebpb, Pparg, and Zfp467, which are adipocyte markers, decreased in this population. Consistent with these results, iPTH treatment inhibited 5-fluorouracil- or ovariectomy (OVX)-induced LepR+MSPC-derived adipogenesis in BM and increased LepR+MSPC-derived osteoblasts, even under the adipocyte-induced conditions. Treatment of OVX rats with iPTH significantly affected the osteoporotic bone tissue and expansion of the BM adipose tissue. These results indicated that iPTH treatment induced transient proliferation of the LepR+MSPCs and skewed their lineage differentiation from adipocytes toward osteoblasts, resulting in an expanded, quiescent, and mature osteoblast population. © 2019 American Society for Bone and Mineral Research.

  • 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年03月

    ISSN  87563282

    　概要を見る

    © 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.

  • Bone Marrow Cells Inhibit BMP-2-Induced Osteoblast Activity in the Marrow Environment

    Nguyen H.T., Ono M., Oida Y., Hara E.S., Komori T., Akiyama K., Nguyen H.T.T., Aung K.T., Pham H.T., Tosa I., Takarada T., Matsuo K., Mizoguchi T., Oohashi T., Kuboki T.

    Journal of Bone and Mineral Research （Journal of Bone and Mineral Research)  34 （ 2 ） 327 - 332 2019年02月

    ISSN  08840431

    　概要を見る

    © 2018 American Society for Bone and Mineral Research Bone morphogenetic protein 2 (BMP-2) is widely known as a potent growth factor that promotes bone formation. However, an increasing number of studies have demonstrated side effects of BMP-2 therapy. A deeper understanding of the effect of BMP-2 on cells other than those involved directly in bone remodeling is of fundamental importance to promote a more effective delivery of BMP-2 to patients. In this study, we aimed to investigate the effect of BMP-2 in the marrow environment. First, BMP-2 adsorbed onto titanium implants was delivered at the tooth extraction socket (marrow-absent site) or in the mandible marrow of beagle dogs. BMP-2 could induce marked bone formation around the implant at the tooth extraction socket. Surprisingly, however, no bone formation was observed in the BMP-2-coated titanium implants inserted in the mandible marrow. In C57BL/6 mice, BMP-2 adsorbed in freeze-dried collagen pellets could induce bone formation in marrow-absent calvarial bone. However, similar to the canine model, BMP-2 could not induce bone formation in the femur marrow. Analysis of osteoblast differentiation using Col1a1(2.3)-GFP transgenic mice revealed a scarce number of osteoblasts in BMP-2-treated femurs, whereas in the control group, osteoblasts were abundant. Ablation of femur marrow recovered the BMP-2 ability to induce bone formation. In vitro experiments analyzing luciferase activity of C2C12 cells with the BMP-responsive element and alkaline phosphatase activity of MC3T3-E1 osteoblasts further revealed that bone marrow cells inhibit the BMP-2 effect on osteoblasts by direct cell–cell contact. Collectively, these results showed that the effect of BMP-2 in inducing bone formation is remarkably repressed by marrow cells via direct cell–cell contact with osteoblasts; this opens new perspectives on the clarification of the side-effects associated with BMP-2 application. © 2018 American Society for Bone and Mineral Research.

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

    Sasaki M., Chubachi S., Kameyama N., Sato M., Haraguchi M., Miyazaki M., Takahashi S., Nakano T., Kuroda Y., Betsuyaku T., Matsuo K.

    PLoS ONE （PLoS ONE)  13 （ 1 ）  2018年01月

    ISSN  1932-6203

    　概要を見る

    Copyright: © 2018 Sasaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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.

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

    松尾 光一

    Australian New Zealand Bone & Mineral Society Annual Scientific Meeting (Hobart, Tasmania) , 

    2015年11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

    Annual Meeting of the American Society for Bone and Mineral Research (Seattle, Washington, USA) , 

    2015年10月
    , 

    ポスター発表

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

    松尾 光一

    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

    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

    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

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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

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担当授業科目 【 表示 ／ 非表示 】

  • 分子細胞生物学

    2024年度

  • 微生物学

    2024年度

  • メディカル・プロフェッショナリズムⅢ

    2024年度

  • 医学概論

    2024年度

  • 学外特別研修（インターンシップ）

    2024年度

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担当経験のある授業科目 【 表示 ／ 非表示 】

  • 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

  • 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

    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

    　
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