KEIO RESEARCHERS INFORMATION SYSTEM

Profile Summary 【 Display / hide 】

Profile Summary 【 Display / hide 】

• Lab of Cell and Tissue Biology (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。

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2001.04

  -

  2002.03

  Chief, National Institute for Longevity Sciences, Chief

• 2002.04

  -

  2007.03

  Associate Professor, School of Medicine, Keio University, Department of Microbiology and Immunology, Associate professor

• 2007.04

  -

  2009.05

  Keio University School of Medicine, Department of Microbiology and Immunology, Associate Professor

• 2009.06

  -

  Present

  Keio University School of Medicine, Laboratory of Cell and Tissue Biology, Professor

• 2009.10

  -

  Present

  総合医科学研究センター長

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• M.D., Ph.D., Keio University, Coursework, 1992.09

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• 医師免許証, 1986.06

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Bone Metabolism

• Osteoimmunology

• Life Science / Cell biology (Cell Biology)

• Life Science / Anatomy (General Anatomy(includes Histology/Embryology))

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• osteoclast

• auditory ossicles

• bone modeling

• bone remodeling

• osteocyte

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Research Themes 【 Display / hide 】

Research Themes 【 Display / hide 】

• 内軟骨性骨化における骨形成性血管の解析, 

  2015.04

  -

  Present

• 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

  -

  Present

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• 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 2026.12

  　View Summary

  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.

  • Access to Document (DOI)

• 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 )  2026.02

  　View Summary

  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.

  • Access to Document (DOI)

• 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 )  2025.12

  　View Summary

  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^Em2/Em2 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^Em2/Em2 cochlea. Female Slc12a2^Em2/+ mice also exhibited mild elevation of ABR thresholds in several sound frequencies. Slc12a2^Em1/Em1 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^Em2 mouse is proposed as a model for studying DFNA78 pathology.

  • Access to Document (DOI)

• 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 )  2025.12

  　View Summary

  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.

  • Access to Document (DOI)

• 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 2025.06

  　View Summary

  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.

  • Access to Document (DOI)

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

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

• Osteogenic capillaries : new aspect of endochondral ossification

  Matsuo, Kōichi

  科学研究費補助金研究成果報告書 2020

• Elucidating mechanisms of altered bone matrix mineralization

  Matsuo, Koichi

  科学研究費補助金研究成果報告書 2015

• Elucidating mechanisms of non-cell-autonomous osteoblast activation

  Matsuo, Koichi

  科学研究費補助金研究成果報告書 2015

• Analysis on the number of osteoclasts in auditory ossicles in middle ea disease and middle ear development

  Matsuo, Koichi

  科学研究費補助金研究成果報告書 2014

• In search for shared regulatory mechanisims of bone mineralization in vertebrates

  Matsuo, Koichi

  科学研究費補助金研究成果報告書 2013

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Bone Cell Biology Assessed by Microscopic Approach. Regulation of bone mineralization through the osteocyte lacuno-canalicular network

  Matsuo Koichi

  Clinical calcium 25 ( 10 ) 1461 - 1466 2015.10

  Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Single Work,  ISSN  0917-5857

  　View Summary

  <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>

• [Glucocorticoid and Bone. Osteocytic osteolysis：potential modulation by glucocorticoids.

  Matsuo Koichi

  Clinical calcium 24 ( 9 ) 1337 - 1342 2014.09

  Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Single Work,  ISSN  0917-5857

  • Access to Document (DOI)

• [Osteoimmunologic regulation of aging].

  Matsuo Koichi

  Clinical calcium 23 ( 1 ) 59 - 64 2013.01

  Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Single Work,  ISSN  0917-5857

  　View Summary

  <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>

• Regulation of bone metabolism by Eph-ephrin family members

  Matsuo K、, Otaki N

  Clinical calcium 22 ( 11 ) 1669 - 1675 2012.11

  Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media), Joint Work,  ISSN  0917-5857

• [Osteocytic osteolysis

  Matsuo Koichi, Nango Nobuhito

  Clinical calcium 22 ( 5 ) 677 - 683 2012.05

  Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media),  ISSN  0917-5857

  　View Summary

  <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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Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

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

  Igarashi Atsushi, Matsuo Koichi, Ueda Shintaroh

  [International presentation]  Australian New Zealand Bone & Mineral Society Annual Scientific Meeting (Hobart, Tasmania) , 

  2015.11

  , 

  Poster presentation

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

  Kuroda Yukiko, Kuno Atsushi, Narimatsu Hisashi,Matsuo Koichi

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

  2015.10

  , 

  Poster presentation

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

  Matsuo Koichi

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

  2015.10

  , 

  Poster presentation

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

  Nango Nobuhito, Kubota Shogo, Yashiro Wataru, Momose Atsushi, Ichinose Shizuko,Matsuo Koichi

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

  2015.10

  , 

  Poster presentation

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

  Matsuo Koichi

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

  2015.10

  , 

  Poster presentation

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

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

• Construction technique for a bilateral skeleton composed of homochiral building blocks

  2021.09

  -

  2023.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, 学術変革領域研究(A), Principal investigator

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

  2021.04

  -

  2025.03

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

• Osteogenic capillaries - new aspect of endochondral ossification

  2017.04

  -

  2021.03

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

Awards 【 Display / hide 】

Awards 【 Display / hide 】

• Distinguished Scientist Award

  2014.07, Japanese Society for Bone and Mineral Research

• Kitasato Award

  2003.06, Keio University School of Medicine

• Young Investigator Award

  1997.09, American Society for Bone and Mineral Research

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• ANATOMY

  2026

• MICROBIOLOGY

  2026

• MEDICAL PROFESSIONALISM 3

  2026

• MOLECULAR CELL BIOLOGY

  2025

• MICROBIOLOGY

  2025

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Courses Previously Taught 【 Display / hide 】

Courses Previously Taught 【 Display / hide 】

• Microbiology

  Keio University

  2015.04

  -

  2016.03

  , 

  Spring Semester, Lecture

• Medical Professionalism III (Research Ethics)

  Keio University

  2015.04

  -

  2016.03

  , 

  Spring Semester, Lecture

• Molecular Cell Biology (MCB) II

  Keio University

  2015.04

  -

  2016.03

  , 

  Spring Semester, Lecture

• Molecular Cell Biology (MCB) II

  Keio University

  2014.04

  -

  2015.03

  , 

  Spring Semester, Lecture

• Microbiology

  Keio University

  2014.04

  -

  2015.03

  , 

  Spring Semester, Lecture

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Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• The Japanese Society for Bone and Mineral Research

  　

• American Society for Bone and Mineral Research (ASBMR)

  　

• International Bone and Mineral Metabolism (IBMS)