Updated on 2025/06/13

写真a

 
HARA EMILIO SATOSHI
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Assistant Professor
Position
Assistant Professor
External link

Degree

  • 博士（歯学） ( 岡山大学 )

Research Interests

  • 生体材料

  • Tissue Engineering

  • Biomaterials

  • Cartilage and Bone Metabolism

  • Biomineralization

Research Areas

  • Nanotechnology/Materials / Chemistry and chemical methodology of biomolecules

  • Life Science / Regenerative dentistry and dental engineering

  • Life Science / Biomedical engineering

Education

  • Okayama University   大学院医歯薬学総合研究科 博士（歯学）  

    2009.10 - 2013.3

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  • Okayama University   歯学部（研究生）  

    2003.10 - 2005.3

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  • Sao Paulo University   School of Dentistry  

    1999.2 - 2003.8

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Research History

  • Advanced Research Center for Oral and Craniofacial Sciences   (Research Associate Professor PI)

    2023.2

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  • 岡山大学 大学院医歯薬学総合研究科   （研究准教授）

    2020.5

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  • Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences   Department of Biomaterials

    2016.4 - 2020.4

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  • Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences   Department of Biomaterials

    2014.4 - 2016.3

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  • Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences   Department of Oral Rehabilitation and Regenerative Medicine

    2013.4 - 2014.3

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  • University of Sao Paulo   FFO

    2005.4 - 2009.3

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Professional Memberships

  • Japanese Society for Dental Materials and Devices

    2014.10

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  • Japanese Society for Biomaterials

    2014.8

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  • International Association for Dental Research

    2010.2

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Papers

  • The cell membrane as biofunctional material for accelerated bone repair. Reviewed International journal

    Emi Hatano, Nahid Akhter, Risa Anada, Mitsuaki Ono, Toshitaka Oohashi, Takuo Kuboki, Hiroshi Kamioka, Masahiro Okada, Takuya Matsumoto, Emilio Satoshi Hara

    Acta biomaterialia   2024.7

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    The cell (plasma) membrane is enriched with numerous receptors, ligands, enzymes, and phospholipids that play important roles in cell-cell and cell-extracellular matrix interactions governing, for instance, tissue development and repair. We previously showed that plasma membrane nanofragments (PMNFs) act as nucleation sites for bone formation in vivo, and induce in vitro mineralization within 1 day. In this study, we optimized the methods for generating, isolating, and applying PMNFs as a cell-free therapeutic to expedite bone defect repair. The PMNFs were isolated from different mouse cell lines (chondrocytes, osteoblasts, and fibroblasts), pre-conditioned, lyophilized, and subsequently transplanted into 2 mm critical-sized calvarial defects in mice (n = 75). The PMNFs from chondrocytes, following a 3-day pre-incubation, significantly accelerated bone repair within 2 weeks, through a coordinated attraction of macrophages, endothelial cells, and osteoblasts to the healing site. In vitro experiments confirmed that PMNFs enhanced cell adhesion. Comparison of the PMNF efficacy with phosphatidylserine, amorphous calcium phosphate (ACP), and living cells confirmed the unique ability of PMNFs to promote accelerated bone repair. Importantly, PMNFs promoted nearly complete integration of the regenerated bone with native tissue after 6 weeks (% non-integrated bone area = 15.02), contrasting with the partial integration (% non-integrated bone area = 56.10; p < 0.01, Student's test) with transplantation of ACP. Vickers microhardness tests demonstrated that the regenerated bone after 6 weeks (30.10 ± 1.75) exhibited hardness similar to native bone (31.07 ± 2.46). In conclusion, this is the first study to demonstrate that cell membrane can be a promising cell-free material with multifaceted biofunctional properties that promote accelerated bone repair. STATEMENT OF SIGNIFICANCE.

    DOI： 10.1016/j.actbio.2024.07.037

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  • Re-Evaluation of Initial Bone Mineralization from an Engineering Perspective Reviewed International journal

    Emilio Satoshi Hara, Masahiro Okada, Noriyuki Nagaoka, Takayoshi Nakano, Takuya Matsumoto

    Tissue Engineering Part B: Reviews   28 ( 1 )   246 - 255   2022.2

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Mary Ann Liebert Inc  

    Bone regeneration was one of the earliest fields to develop in the context of tissue regeneration, and currently, repair of small-sized bone defects has reached a high success rate. Future researches are expected to incorporate more advanced techniques toward achieving rapid bone repair and modulation of the regenerated bone quality. For these purposes, it is important to have a more integrative understanding of the mechanisms of bone formation and maturation from multiple perspectives and to incorporate these new concepts into the development and designing of novel materials and techniques for bone regeneration. This review focuses on the analysis of the earliest stages of bone tissue development from the biology, material science, and engineering perspectives for a more integrative understanding of bone formation and maturation, and for the development of novel biology-based engineering approaches for tissue synthesis in vitro. More specifically, the authors describe the systematic methodology that allowed the understanding of the different nucleation sites in intramembranous and endochondral ossification, the space-making process for mineral formation and growth, as well as the process of apatite crystal cluster growth in vivo in the presence of suppressing biomolecules. Impact Statement A detailed understanding of the developmental process of bone tissue leads to the acquisition of useful information for the bone tissue fabrication. This review summarizes the study of the calcification process of the calvaria and epiphyses from an engineering perspective and provides useful information for the realization of bone tissue biofabrication. Here, we describe the new mechanism of space formation for mineralization such as rupture of chondrocytes and disruption of cell-cell adhesion. We also describe the roles of nucleation site such as cell membrane nanofragments and matrix vesicles.

    DOI： 10.1089/ten.teb.2020.0352

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    Other Link： https://www.liebertpub.com/doi/pdf/10.1089/ten.teb.2020.0352

  • Biohybrid Variable‐Stiffness Soft Actuators that Self‐Create Bone Reviewed

    Danfeng Cao, Jose G. Martinez, Emilio Satoshi Hara, Edwin W. H. Jager

    Advanced Materials   34 ( 8 )   2107345 - 2107345   2022.2

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    DOI： 10.1002/adma.202107345

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    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/adma.202107345

  • Effect of Biomechanical Environment on Degeneration of Meckel’s Cartilage Reviewed

    Mahmoud Farahat, Gulsan A.S. Kazi, Emilio S. Hara, Takuya Matsumoto

    Journal of Dental Research   100 ( 2 )   171 - 178   2021.2

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    Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

    During orofacial tissue development, the anterior and posterior regions of the Meckel’s cartilage undergo mineralization, while the middle region undergoes degeneration. Despite the interesting and particular phenomena, the mechanisms that regulate the different fates of Meckel’s cartilage, including the effects of biomechanical cues, are still unclear. Therefore, the purpose of this study was to systematically investigate the course of Meckel’s cartilage during embryonic development from a biomechanical perspective. Histomorphological and biomechanical (stiffness) changes in the Meckel’s cartilage were analyzed from embryonic day 12 to postnatal day 0. The results revealed remarkable changes in the morphology and size of chondrocytes, as well as the occurrence of chondrocyte burst in the vicinity of the mineralization site, an often-seen phenomenon preceding endochondral ossification. To understand the effect of biomechanical cues on Meckel’s cartilage fate, a mechanically tuned 3-dimensional hydrogel culture system was used. At the anterior region, a moderately soft environment (10-kPa hydrogel) promoted chondrocyte burst and ossification. On the contrary, at the middle region, a more rigid environment (40-kPa hydrogel) enhanced cartilage degradation by inducing a higher expression of MMP-1 and MMP-13. These results indicate that differences in the biomechanical properties of the surrounding environment are essential factors that distinctly guide the mineralization and degradation of Meckel’s cartilage and would be valuable tools for modulating in vitro cartilage and bone tissue engineering.

    DOI： 10.1177/0022034520960118

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    Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/0022034520960118

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

    Ha Thi Nguyen, Mitsuaki Ono, Yasutaka Oida, Emilio Satoshi Hara, Taishi Komori, Kentaro Akiyama, Ha Thi Thu Nguyen, Kyaw Thu Aung, Hai Thanh Pham, Ikue Tosa, Takeshi Takarada, Koichi Matsuo, Toshihide Mizoguchi, Toshitaka Oohashi, Takuo Kuboki

    Journal of Bone and Mineral Research   34 ( 2 )   327 - 332   2019.2

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    DOI： 10.1002/jbmr.3598

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    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jbmr.3598

  • Rapid bioinspired mineralization using cell membrane nanofragments and alkaline milieu Reviewed

    Emilio Satoshi Hara, Masahiro Okada, Takuo Kuboki, Takayoshi Nakano, Takuya Matsumoto

    Journal of Materials Chemistry B   6 ( 38 )   6153 - 6161   2018.9

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1039/c8tb01544a

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  • Bioinspired Mineralization Using Chondrocyte Membrane Nanofragments Reviewed International journal

    Emilio Satoshi Hara, Masahiro Okada, Noriyuki Nagaoka, Takako Hattori, Takuo Kuboki, Takayoshi Nakano, Takuya Matsumoto

    ACS Biomaterials Science & Engineering   4 ( 2 )   617 - 625   2018.2

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

    DOI： 10.1021/acsbiomaterials.7b00962

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  • Biocompatible nanostructured solid adhesives for biological soft tissues Reviewed

    Okada, M., Nakai, A., Hara, E.S., Taguchi, T., Nakano, T., Matsumoto, T.

    Acta Biomaterialia   57   404 - 413   2017

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

    DOI： 10.1016/j.actbio.2017.05.014

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  • Fluocinolone Acetonide Is a Potent Synergistic Factor of TGF‐β3–Associated Chondrogenesis of Bone Marrow–Derived Mesenchymal Stem Cells for Articular Surface Regeneration Reviewed

    Emilio Satoshi Hara, Mitsuaki Ono, Hai Thanh Pham, Wataru Sonoyama, Satoshi Kubota, Masaharu Takigawa, Takuya Matsumoto, Marian F Young, Bjorn R Olsen, Takuo Kuboki

    Journal of Bone and Mineral Research   30 ( 9 )   1585 - 1596   2015.9

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/jbmr.2502

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    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jbmr.2502

  • Novel chondrogenic and chondroprotective effects of the natural compound harmine Reviewed

    Emilio Satoshi Hara, Mitsuaki Ono, Satoshi Kubota, Wataru Sonoyama, Yasutaka Oida, Takako Hattori, Takashi Nishida, Takayuki Furumatsu, Toshifumi Ozaki, Masaharu Takigawa, Takuo Kuboki

    Biochimie   95 ( 2 )   374 - 381   2013.2

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.biochi.2012.10.016

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  • BMP-2 generates a functional bone marrow niche by inducing the differentiation of local mesenchymal cells into CAR cells

    Ikue Tosa, Mitsuaki Ono, Anh Tuan Dang, Ziyi Wang, Maiko Kimura, Wakana Kitagawa, Kei Ishibashi, Hang Thuy Do, Kun Zhao, Emilio Satoshi Hara, Noboru Asada, Takashi Nagasawa, Toshitaka Oohashi, Naoya Ohara, Takuo Kuboki

    Blood Advances   2025.3

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.1182/bloodadvances.2024014062

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  • Local E-rhBMP-2/β-TCP Application Rescues Osteocyte Dendritic Integrity and Reduces Microstructural Damage in Alveolar Bone Post-Extraction in MRONJ-like Mouse Model Reviewed

    Anh Tuan Dang, Mitsuaki Ono, Ziyi Wang, Ikue Tosa, Emilio Satoshi Hara, Akihiro Mikai, Wakana Kitagawa, Tomoko Yonezawa, Takuo Kuboki, Toshitaka Oohashi

    International Journal of Molecular Sciences   25 ( 12 )   6648 - 6648   2024.6

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    Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/β-Tricalcium phosphate (E-rhBMP-2/β-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/β-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/β-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/β-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ.

    DOI： 10.3390/ijms25126648

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  • Electrochemical control of bone microstructure on electroactive surfaces for modulation of stem cells and bone tissue engineering Reviewed International journal

    Danfeng Cao, Jose G. Martinez, Risa Anada, Emilio Satoshi Hara, Hiroshi Kamioka, Edwin W. H. Jager

    Science and Technology of Advanced Materials   24 ( 1 )   2183710 - 2183710   2023.12

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    Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    Controlling stem cell behavior at the material interface is crucial for the development of novel technologies in stem cell biology and regenerative medicine. The composition and presentation of bio-factors on a surface strongly influence the activity of stem cells. Herein, we designed an electroactive surface that mimics the initial process of trabecular bone formation, by immobilizing chondrocyte-derived plasma membrane nanofragments (PMNFs) on its surface for rapid mineralization within 2 days. Moreover, the electroactive surface was based on the conducting polymer polypyrrole (PPy), which enabled dynamic control of the presentation of PMNFs on the surface via electrochemical redox switching, further resulting in the formation of bone minerals with different morphologies. Furthermore, bone minerals with contrasting surface morphologies had differential effects on the differentiation of human bone marrow-derived stem cells (hBMSCs) cultured on the surface. Together, this electroactive surface showed multifunctional characteristics, not only allowing dynamic control of PMNF presentation but also promoting the formation of bone minerals with different morphologies within 2 days. This electroactive substrate could be valuable for more precise control of stem cell growth and differentiation, and further development of more suitable microenvironments containing bone apatite for housing a bone marrow stem cell niche, such as biochips/bone-on-chips.

    DOI： 10.1080/14686996.2023.2183710

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  • Tunable electroactive biomimetic bone-like surfaces for bone marrow-on-chips Reviewed

    Danfeng Cao, Jose G. Martinez, Laetitia Skalla, Erik Hultin, Jan-Ingvar Jönsson, Risa Anada, Hiroshi Kamioka, Edwin W. H. Jager, Emilio Satoshi Hara

    2023 IEEE BioSensors Conference (BioSensors)   1 - 4   2023.7

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    DOI： 10.1109/biosensors58001.2023.10281047

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  • Variable Stiffness Actuators with Covalently Attached Nanofragments that Induce Mineralization Reviewed International journal

    Danfeng Cao, Jose G. Martinez, Emilio Satoshi Hara, Edwin W. H. Jager

    Advanced Materials Technologies   2201651 - 2201651   2023.4

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    Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    DOI： 10.1002/admt.202201651

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    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/admt.202201651

  • Important roles of odontoblast membrane phospholipids in early dentin mineralization Reviewed International journal

    Risa Anada, Emilio Satoshi Hara, Noriyuki Nagaoka, Masahiro Okada, Hiroshi Kamioka, Takuya Matsumoto

    Journal of Materials Chemistry B   11 ( 3 )   657 - 666   2023.1

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    Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

    The objective of this study was to first identify the timing and location of early mineralization of mouse first molar, and subsequently, to characterize the nucleation site for mineral formation...

    DOI： 10.1039/d2tb02351b

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  • Fabrication of initial trabecular bone inspired three-dimensional structure with cell membrane nanofragments Reviewed

    Koichi Kadoya, Emilio Satoshi Hara, Masahiro Okada, Yu Yang Jiao, Takayoshi Nakano, Akira Sasaki, Takuya Matsumoto

    Regenerative Biomaterials   2022.11

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    Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

    Abstract

    The extracellular matrix of trabecular bone has a large surface exposed to the bone marrow and plays important roles such as hematopoietic stem cell niche formation and maintenance. In vitro reproduction of trabecular bone microenvironment would be valuable not only for developing a functional scaffold for bone marrow tissue engineering but also for understanding its biological functions. Herein, we analyzed and reproduced the initial stages of trabecular bone formation in mouse femur epiphysis. We identified that the trabecular bone formation progressed through the following steps: (1) partial rupture of hypertrophic chondrocytes; (2) calcospherite formation on cell nanofragments (CNFs) derived from the ruptured cell membranes; and (3) calcospherite growth and fusion to form the initial three-dimensional (3D) structure of trabecular bones. For reproducing the initial trabecular bone formation in vitro, we collected CNFs from cultured cells and used as nucleation sites for biomimetic calcospherite formation. Strikingly, almost the same 3D structure of the initial trabecular bone could be obtained in vitro by using additional CNFs as a binder to fuse biomimetic calcospherites.

    DOI： 10.1093/rb/rbac088

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  • Distinct Morphologies of Bone Apatite Clusters in Endochondral and Intramembranous Ossification Reviewed

    Emilio Satoshi Hara, Noriyuki Nagaoka, Masahiro Okada, Takayoshi Nakano, Takuya Matsumoto

    Advanced Biology   6 ( 11 )   2200076 - 2200076   2022.11

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    Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    DOI： 10.1002/adbi.202200076

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    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/adbi.202200076

  • Soft actuators that self-create bone for biohybrid (micro)robotics Reviewed

    Danfeng Cao, Jose G. Martinez, Emilio Satoshi Hara, Edwin W. H. Jager

    2022 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS)   2022.7

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    Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

    DOI： 10.1109/marss55884.2022.9870251

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  • Mechanotransductive Mechanisms of Biomimetic Hydrogel Cues Modulating Meckel's Cartilage Degeneration Reviewed

    Mahmoud Farahat, Emilio S. Hara, Risa Anada, Gulsan A.S. Kazi, Nahid M. Akhter, Takuya Matsumoto

    Advanced Biology   2101315 - 2101315   2022.6

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    Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    DOI： 10.1002/adbi.202101315

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    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/adbi.202101315

  • Self-adhering implantable device of titanium: Enhanced soft-tissue adhesion by sandblast pretreatment Reviewed

    Atsushi Yabe, Masahiro Okada, Emilio Satoshi Hara, Yasuhiro Torii, Takuya Matsumoto

    Colloids and Surfaces B: Biointerfaces   211   112283 - 112283   2022.3

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier {BV}  

    DOI： 10.1016/j.colsurfb.2021.112283

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  • Suppression of Bone Necrosis around Tooth Extraction Socket in a MRONJ-like Mouse Model by E-rhBMP-2 Containing Artificial Bone Graft Administration Reviewed International journal

    Yukie Tanaka, Kyaw Thu Aung, Mitsuaki Ono, Akihiro Mikai, Anh Tuan Dang, Emilio Satoshi Hara, Ikue Tosa, Kei Ishibashi, Aya Ono-Kimura, Kumiko Nawachi, Takuo Kuboki, Toshitaka Oohashi

    International Journal of Molecular Sciences   22 ( 23 )   12823 - 12823   2021.11

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    Medication-related osteonecrosis of the jaw (MRONJ) is related to impaired bone healing conditions in the maxillomandibular bone region as a complication of bisphosphonate intake. Although there are several hypotheses for the onset of MRONJ symptoms, one of the possible causes is the inhibition of bone turnover and blood supply leading to bone necrosis. The optimal treatment strategy for MRONJ has not been established either. BMP-2, a member of the TGF-β superfamily, is well known for regulating bone remodeling and homeostasis prenatally and postnatally. Therefore, the objectives of this study were to evaluate whether cyclophosphamide/zoledronate (CY/ZA) induces necrosis of the bone surrounding the tooth extraction socket, and to examine the therapeutic potential of BMP-2 in combination with the hard osteoinductive biomaterial, β-tricalcium phosphate (β-TCP), in the prevention and treatment of alveolar bone loss around the tooth extraction socket in MRONJ-like mice models. First, CY/ZA was intraperitoneally administered for three weeks, and alveolar bone necrosis was evaluated before and after tooth extraction. Next, the effect of BMP-2/β-TCP was investigated in both MRONJ-like prevention and treatment models. In the prevention model, CY/ZA was continuously administered for four weeks after BMP-2/β-TCP transplantation. In the treatment model, CY/ZA administration was suspended after transplantation of BMP-2/β-TCP. The results showed that CY/ZA induced a significant decrease in the number of empty lacunae, a sign of bone necrosis, in the alveolar bone around the tooth extraction socket after tooth extraction. Histological analysis showed a significant decrease in the necrotic alveolar bone around tooth extraction sockets in the BMP-2/β-TCP transplantation group compared to the non-transplanted control group in both MRONJ-like prevention and treatment models. However, bone mineral density, determined by micro-CT analysis, was significantly higher in the BMP-2/β-TCP transplanted group than in the control group in the prevention model only. These results clarified that alveolar bone necrosis around tooth extraction sockets can be induced after surgical intervention under CY/ZA administration. In addition, transplantation of BMP-2/β-TCP reduced the necrotic alveolar bone around the tooth extraction socket. Therefore, a combination of BMP-2/β-TCP could be an alternative approach for both prevention and treatment of MRONJ-like symptoms.

    DOI： 10.3390/ijms222312823

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  • Immediate soft-tissue adhesion and the mechanical properties of the Ti–6Al–4V alloy after long-term acid treatment Reviewed International journal

    Yaming Wang, Masahiro Okada, Shi Chao Xie, Yu Yang Jiao, Emilio Satoshi Hara, Hiroaki Yanagimoto, Takumi Fukumoto, Takuya Matsumoto

    Journal of Materials Chemistry B   9 ( 39 )   8348 - 8354   2021.8

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

    A metallic solid-state adhesive for biological soft tissues was fabricated using Ti–6Al–4V alloys, and the influence of the minor β phase and the small amount of Al in the α phase are reported.

    DOI： 10.1039/d1tb00919b

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  • Nanostructural analysis of distinct nucleation sites in pathological mineralization Reviewed

    Emilio Satoshi Hara, Susumu Oozawa, Noriyuki Nagaoka, Masahiro Okada, Shingo Kasahara, Takuya Matsumoto

    Materials Advances   2 ( 13 )   4423 - 4431   2021.6

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    Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1039/d1ma00273b

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  • Preclinical bioequivalence study of E.coli-derived rhBMP-2/β-TCP and autogenous bone in a canine guided-bone regeneration model. Reviewed

    Shuji Nosho, Mitsuaki Ono, Taishi Komori, Akihiro Mikai, Ikue Tosa, Kei Ishibashi, Yukie Tanaka, Aya Kimura-Ono, Emilio S Hara, Toshitaka Oohashi, Takuo Kuboki

    Journal of Prosthodontic Research   66 ( 1 )   124 - 130   2021.6

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Prosthodontic Society  

    PURPOSE: Bone morphogenetic protein (BMP)-2 is a potent growth factor that is widely used in the orthopedic and dental fields for bone regeneration.However, recombinant human BMP-2 (rhBMP-2) products have not been legally approved in Japan. Recently, our research group succeeded in producing GMP-grade rhBMP-2 using the E. coli system (E-rhBMP-2) at the industrial level and developed E-rhBMP-2 adsorbed onto β-TCP (E-rhBMP-2/β-TCP) as an alternative material to autogenous bone grafts. Previous studies on the toxicity, pharmacokinetics, and optimal doses of E-rhBMP-2 have confirmed its safety and efficiency. However, comparative studies with standard treatment therapies are still necessary before clinical application in humans. Therefore, in this preclinical study, we compared the bone regeneration ability of E-rhBMP-2/β-TCP and autogenous bone grafts in a canine guided-bone regeneration model. METHODS: Following extraction of the maxillary third premolar, box-type bone defects (10 mmL × 4 mmW × 9 mmH) were created in the extraction socket area and transplanted with E-rhBMP-2/β-TCP or autogenous bone graft in a canine. After 8 weeks, micro-CT and histological analyses were performed. RESULTS: Transplantation of both E-rhBMP-2/β-TCP and autogenous bone graft significantly promoted bone formation compared to the non-transplantation control group. The bone formation ability of E-rhBMP-2/β-TCP was equal to that of the autogenous bone graft. Histological analysis showed that excessive infiltration of inflammatory cells and residual β-TCP particles mostly were not observed in the E-rhBMP-2/β-TCP transplantation group. CONCLUSIONS: This preclinical study demonstrated that E-rhBMP-2/β-TCP and autogenous bone have equal potential to promote bone regeneration.

    DOI： 10.2186/jpr.jpr_d_20_00226

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  • Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo Reviewed

    Hai Pham, Mitsuaki Ono, Emilio S. Hara, Ha Nguyen, Anh Dang, Hang Do, Taishi Komori, Ikue Tosa, Yuri Hazehara-Kunitomo, Yuya Yoshioka, Yasutaka Oida, Kentaro Akiyama, Takuo Kuboki

    Materials   14 ( 1 )   208 - 208   2021.1

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    Authorship：Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    Aging tissues present a progressive decline in homeostasis and regenerative capacities, which has been associated with degenerative changes in tissue-specific stem cells and stem cell niches. We hypothesized that amino acids could regulate the stem cell phenotype and differentiation ability of human bone marrow-derived mesenchymal stromal cells (hBMSCs). Thus, we performed a screening of 22 standard amino acids and found that D-tryptophan (10 μM) increased the number of cells positive for the early stem cell marker SSEA-4, and the gene expression levels of OCT-4, NANOG, and SOX-2 in hBMSCs. Comparison between D- and L-tryptophan isomers showed that the latter presents a stronger effect in inducing the mRNA levels of Oct-4 and Nanog, and in increasing the osteogenic differentiation of hBMSCs. On the other hand, L-tryptophan suppressed adipogenesis. The migration and colony-forming ability of hBMSCs were also enhanced by L-tryptophan treatment. In vivo experiments delivering L-tryptophan (50 mg/kg/day) by intraperitoneal injections for three weeks confirmed that L-tryptophan significantly increased the percentage of cells positive for SSEA-4, mRNA levels of Nanog and Oct-4, and the migration and colony-forming ability of mouse BMSCs. L-kynurenine, a major metabolite of L-tryptophan, also induced similar effects of L-tryptophan in enhancing stemness and osteogenic differentiation of BMSCs in vitro and in vivo, possibly indicating the involvement of the kynurenine pathway as the downstream signaling of L-tryptophan. Finally, since BMSCs migrate to the wound healing site to promote bone healing, surgical defects of 1 mm in diameter were created in mouse femur to evaluate bone formation after two weeks of L-tryptophan or L-kynurenine injection. Both L-tryptophan and L-kynurenine accelerated bone healing compared to the PBS-injected control group. In summary, L-tryptophan enhanced the stemness and osteoblastic differentiation of BMSCs and may be used as an essential factor to maintain the stem cell properties and accelerate bone healing and/or prevent bone loss.

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  • Micro-Architectural Investigation of Teleost Fish Rib Inducing Pliant Mechanical Property Reviewed International journal

    Yu Yang Jiao, Masahiro Okada, Emilio Satoshi Hara, Shi Chao Xie, Noriyuki Nagaoka, Takayoshi Nakano, Takuya Matsumoto

    Materials   13 ( 22 )   5099 - 5099   2020.11

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    Despite the fact that various reports have been discussing bone tissue regeneration, precise bone tissue manipulation, such as controlling the physical properties of the regenerated bone tissue, still remains a big challenge. Here, we focused on the teleost fish ribs showing flexible and tough mechanical properties to obtain a deeper insight into the structural and functional features of bone tissue from different species, which would be valuable for the superior design of bone-mimicking materials. Herein, we examined their compositions, microstructure, histology, and mechanical properties. The first rib of Carassius langsdorfii showed a higher Young’s modulus with a small region of chondrocyte clusters compared with other smaller ribs. In addition, highly oriented collagen fibers and osteocytes were observed in the first rib, indicating that the longest first rib would be more mature. Moreover, the layer-by-layer structure of the oriented bone collagen was observed in each rib. These microarchitectural and compositional findings of fish rib bone would give one the useful idea to reproduce such a highly flexible rib bone-like material.

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  • Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model Reviewed

    Kyaw Thu Aung, Kentaro Akiyama, Masayoshi Kunitomo, Aung Ye Mun, Ikue Tosa, Ha Thi Thu Nguyen, Jiewen Zhang, Teisaku Kohno, Mitsuaki Ono, Emilio Satoshi Hara, Takuo Kuboki

    International Journal of Molecular Sciences   21 ( 21 )   8103 - 8103   2020.10

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  • Distinct Osteogenic Potentials of BMP-2 and FGF-2 in Extramedullary and Medullary Microenvironments Reviewed

    Shuji Nosho, Ikue Tosa, Mitsuaki Ono, Emilio Satoshi Hara, Kei Ishibashi, Akihiro Mikai, Yukie Tanaka, Aya Kimura-Ono, Taishi Komori, Kenji Maekawa, Takuo Kuboki, Toshitaka Oohashi

    International Journal of Molecular Sciences   21 ( 21 )   7967 - 7967   2020.10

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  • BMP-2/β-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model Reviewed

    Akihiro Mikai, Mitsuaki Ono, Ikue Tosa, Ha Thi Thu Nguyen, Emilio Satoshi Hara, Shuji Nosho, Aya Kimura-Ono, Kumiko Nawachi, Takeshi Takarada, Takuo Kuboki, Toshitaka Oohashi

    International Journal of Molecular Sciences   21 ( 19 )   7028 - 7028   2020.9

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  • Cellular Fragments as Biomaterial for Rapid In Vitro Bone-Like Tissue Synthesis Reviewed

    Mst Nahid Akhter, Emilio Hara, Koichi Kadoya, Masahiro Okada, Takuya Matsumoto

    International Journal of Molecular Sciences   21 ( 15 )   5327 - 5327   2020.7

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    Current stem cell-based techniques for bone-like tissue synthesis require at least two to three weeks. Therefore, novel techniques to promote rapid 3D bone-like tissue synthesis in vitro are still required. In this study, we explored the concept of using cell nanofragments as a substrate material to promote rapid bone formation in vitro. The methods for cell nanofragment fabrication were ultrasonication (30 s and 3 min), non-ionic detergent (triton 0.1% and 1%), or freeze-dried powder. The results showed that ultrasonication for 3 min allowed the fabrication of homogeneous nanofragments of less than 150 nm in length, which mineralized surprisingly in just one day, faster than the fragments obtained from all other methods. Further optimization of culture conditions indicated that a concentration of 10 mM or 100 mM of β-glycerophosphate enhanced, whereas fetal bovine serum (FBS) inhibited in a concentration-dependent manner, the mineralization of the cell nanofragments. Finally, a 3D collagen-cell nanofragment-mineral complex mimicking a bone-like structure was generated in just two days by combining the cell nanofragments in collagen gel. In conclusion, sonication for three min could be applied as a novel method to fabricate cell nanofragments of less than 150 nm in length, which can be used as a material for in vitro bone tissue engineering.

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  • Titanium as an Instant Adhesive for Biological Soft Tissue Reviewed

    Masahiro Okada, Emilio Satoshi Hara, Atsushi Yabe, Kei Okada, Yo Shibata, Yasuhiro Torii, Takayoshi Nakano, Takuya Matsumoto

    Advanced Materials Interfaces   7 ( 9 )   1902089 - 1902089   2020.5

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  • Association of masticatory muscle activity with sleep arousal and other concomitant movements during sleep Reviewed

    Haruna Miki, Hajime Minakuchi, Mayu Miyagi, Emilio Satoshi Hara, Shuji Shigemoto, Yoshitaka Suzuki, Kenji Maekawa, Yoshizo Matsuka, Glenn T. Clark, Takuo Kuboki

    Journal of Oral Rehabilitation   2020.3

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    DOI： 10.1111/joor.12913

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  • Vibratory splint therapy for decreasing sleep clenching: A pilot study Reviewed

    Emilio Satoshi Hara, Andrea Lusvarghi Witzel, Hajime Minakuchi, Carlos Eduardo de Pitta, Rosane Tronquin Gallo, Masahiro Okada, Takuya Matsumoto, Takuo Kuboki, Marcelo Costa Bolzan

    CRANIO: The Journal of Craniomandibular & Sleep Practice   38 ( 1 )   15 - 21   2020.1

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    DOI： 10.1080/08869634.2018.1488652

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  • DNA Methylation-Based Regulation of Human Bone Marrow-Derived Mesenchymal Stem/Progenitor Cell Chondrogenic Differentiation Reviewed

    Yu Nomura, Emilio Satoshi Hara, Yuya Yoshioka, Há Thi Nguyen, Shuji Nosho, Taishi Komori, Kei Ishibashi, Toshitaka Oohashi, Mitsuaki Ono, Takuo Kuboki

    Cells Tissues Organs   207 ( 3-4 )   115 - 126   2019.10

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    Stem cells have essential applications in in vitro tissue engineering or regenerative medicine. However, there is still a need to understand more deeply the mechanisms of stem cell differentiation and to optimize the methods to control stem cell function. In this study, we first investigated the activity of DNA methyltransferases (DNMTs) during chondrogenic differentiation of human bone marrow-derived mesenchymal stem/progenitor cells (hBMSCs) and found that DNMT3A and DNMT3B were markedly upregulated during hBMSC chondrogenic differentiation. In an attempt to understand the effect of DNMT3A and DNMT3B on the chondrogenic differentiation of hBMSCs, we transiently transfected the cells with expression vectors for the two enzymes. Interestingly, DNMT3A overexpression strongly enhanced the chondrogenesis of hBMSCs, by increasing the gene expression of the mature chondrocyte marker, collagen type II, more than 200-fold. Analysis of the methylation condition in the cells revealed that DNMT3A and DNMT3B methylated the promoter sequence of early stem cell markers, NANOG and POU5F1(OCT-4). Conversely, the suppression of chondrogenic differentiation and the increase in stem cell markers of hBMSCs were obtained by chemical stimulation with the demethylating agent, 5-azacitidine. Loss-of-function assays with siRNAs targeting DNMT3A also significantly suppressed the chondrogenic differentiation of hBMSCs. Together, these results not only show the critical roles of DNMTs in regulating the chondrogenic differentiation of hBMSCs, but also suggest that manipulation of DNMT activity can be important tools to enhance the differentiation of hBMSCs towards chondrogenesis for potential application in cartilage tissue engineering or cartilage regeneration.

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  • Type XVIII Collagen Modulates Keratohyalin Granule Formation and Keratinization in Oral Mucosa Reviewed

    Ha Thi Thu Nguyen, Mitsuaki Ono, Emilio Hara, Taishi, Midori Edamatsu, Tomoko Yonezawa, Aya Kimura-Ono, Kenji Maekawa, Takuo Kuboki, Toshitaka Oohashi

    International Journal of Molecular Sciences   20 ( 19 )   4739 - 4739   2019.9

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    DOI： 10.3390/ijms20194739

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  • Fibronectin-induced ductal formation in salivary gland self-organization model Reviewed

    Mahmoud Farahat, Gulsan A. S. Kazi, Hiroaki Taketa, Emilio S. Hara, Masamitsu Oshima, Takuo Kuboki, Takuya Matsumoto

    DEVELOPMENTAL DYNAMICS   248 ( 9 )   813 - 825   2019.9

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  • Improvement of mechanical properties of Y-TZP by thermal annealing with monoclinic zirconia nanoparticle coating Reviewed International journal

    Masahiro Okada, Hiroaki Taketa, Emilio Satoshi Hara, Yasuhiro Torii, Masao Irie, Takuya Matsumoto

    Dental Materials   35 ( 7 )   970 - 978   2019.7

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    OBJECTIVE: To assess whether a thermal annealing with a monoclinic zirconia (mZrO2) nanoparticle coating can improve the reliability of sandblasted yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) and maintain its mechanical strength. METHODS: Commercially available Y-TZP (Lava Frame, 3M Dental Products) disks were sintered and surface-treated as follows: AS (as sintered, with no treatment); SB (sandblasting); SB-TA (sandblasting followed by thermal annealing at 1000 °C); and SB-mZr-TA (sandblasting followed by thermal annealing at 1000 °C with the mZrO2 nanoparticle coating). The mZrO2 nanoparticles of 21 nm in size were prepared by a hydrothermal method, and coated onto Y-TZP sintered disks as a 5 g/L ethanol dispersion. Biaxial flexural strength (S) was measured using the piston-on-three-ball test, and reliability was evaluated by the Weibull modulus (m). RESULTS: Biaxial flexural tests showed a significant increase in the strength of Group SB (SSB = 1445 ± 191 MPa) compared with Group AS (SAS = 1071 ± 112 MPa). The thermal annealing improved the reliabilities of the sandblasted Y-TZP (mSB-TA = 20.14 and mSB-mZr-TA = 21.33), as compared with Group SB (mSB = 7.77). However, the conventional thermal annealing without the mZrO2 coating caused a significant decrease in the strength of sandblasted Y-TZP (SSB-TA = 1273 ± 65 MPa). Importantly, the mZrO2 coating prevented the decrease in the strength caused by conventional thermal annealing (SSB-mZr-TA = 1379 ± 65 MPa). SIGNIFICANCE: The thermal annealing with the mZrO2 nanoparticle coating can improve the reliability of sandblasted Y-TZP and maintain its mechanical strength, which would otherwise be decreased by the conventional annealing process.

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  • Biomimetic mineralization using matrix vesicle nanofragments Reviewed

    Yosuke Kunitomi, Emilio Satoshi Hara, Masahiro Okada, Noriyuki Nagaoka, Takuo Kuboki, Takayoshi Nakano, Hiroshi Kamioka, Takuya Matsumoto

    Journal of Biomedical Materials Research Part A   107 ( 5 )   1021 - 1030   2019.5

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    DOI： 10.1002/jbm.a.36618

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  • Intermediate Water on Calcium Phosphate Minerals: Its Origin and Role in Crystal Growth Reviewed

    Masahiro Okada, Emilio Satoshi Hara, Daisuke Kobayashi, Shoki Kai, Keiko Ogura, Masaru Tanaka, Takuya Matsumoto

    ACS Applied Bio Materials   2019.3

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    DOI： 10.1021/acsabm.9b00014

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  • Acidic Pre-Conditioning Enhances the Stem Cell Phenotype of Human Bone Marrow Stem/Progenitor Cells Reviewed

    Yuri Hazehara-Kunitomo, Emilio S. Hara, Mitsuaki Ono, Kyaw Aung, Keiko Komi, Hai Pham, Kentaro Akiyama, Masahiro Okada, Toshitaka Oohashi, Takuya Matsumoto, Takuo Kuboki

    International Journal of Molecular Sciences   20 ( 5 )   1097 - 1097   2019.3

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  • 骨組織発生の材料学的再検討が新しい骨組織工学につながる

    松本卓也, HARA ES

    バイオマテリアル   37 ( 1 )   50 - 51   2019

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  • New Functions of Classical Compounds against Orofacial Inflammatory Lesions Reviewed

    Norifumi Moritani, Emilio Hara, Satoshi Kubota

    Medicines   5 ( 4 )   118 - 118   2018.11

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    Anti-inflammatory agents have been widely used to ameliorate severe inflammatory symptoms of a number of diseases, and such therapeutics are particularly useful for diseases with intolerable pain without significant mortality. A typical example of this is a disease known as stomatitis; although stomatitis itself is not a life-threatening disease, it severely impairs the individual’s quality of life, and thus a standard therapeutic strategy for it has already been established. The topical application of a bioactive agent is quite easy, and a strong anti-inflammatory agent can be used without significant adverse effects. In contrast, natural products with relatively mild bioactivity are used for systemic intervention. However, new aspects of classical drugs used in these established therapeutic methods have recently been discovered, which is expanding the utility of these compounds to other oral diseases such as osteoarthritis of temporomandibular joints (TMJ-OA). In this review article, after summarizing the general concept and pathobiology of stomatitis, its established therapeutics are explained. Thereafter, recent advances in the research into related compounds, which is uncovering new biological functions of the agents used therein, are introduced. Indeed, regenerative therapeutics for TMJ-OA may be developed with the classical compounds currently being used.

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  • CCN4/WISP1 controls cutaneous wound healing by modulating proliferation, migration and ECM expression in dermal fibroblasts via α5β1 and TNFα Reviewed

    Mitsuaki Ono, Asuka Masaki, Azusa Maeda, Tina M. Kilts, Emilio S. Hara, Taishi Komori, Hai Pham, Takuo Kuboki, Marian F. Young

    Matrix Biology   68-69   533 - 546   2018.8

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    DOI： 10.1016/j.matbio.2018.01.004

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  • Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium Reviewed

    Taishi Komori, Mitsuaki Ono, Emilio Satoshi Hara, Junji Ueda, Ha Thi Thu Nguyen, Ha Thi Nguyen, Tomoko Yonezawa, Takahiro Maeba, Aya Kimura-Ono, Takeshi Takarada, Ryusuke Momota, Kenji Maekawa, Takuo Kuboki, Toshitaka Oohashi

    Scientific Reports   8 ( 1 )   2018.2

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    DOI： 10.1038/s41598-018-21000-0

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  • Fabrication of Hydroxyapatite Nanofibers with High Aspect Ratio via Low-Temperature Wet Precipitation Methods Under Acidic Conditions: From Molecular and Nano-structural Analyses to Environmental Science Reviewed

    Emilio Hara

    Biomineralization   211 - 218   2018.1

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    DOI： 10.1007/978-981-13-1002-7_22

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  • Chondrocyte burst promotes space for mineral expansion Reviewed

    Emilio Satoshi Hara, Masahiro Okada, Noriyuki Nagaoka, Takako Hattori, Letycia Mary Iida, Takuo Kuboki, Takayoshi Nakano, Takuya Matsumoto

    Integrative Biology   10 ( 1 )   57 - 66   2018.1

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    DOI： 10.1039/c7ib00130d

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  • 差初期石灰化過程を詳細に観察し模倣する

    松本卓也, HARA ES

    化学工業   69 ( 6 )   23 - 28   2018

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  • MCSF orchestrates branching morphogenesis in developing submandibular gland tissue Reviewed

    Sathi, G.A., Farahat, M., Hara, E.S., Taketa, H., Nagatsuka, H., Kuboki, T., Matsumoto, T.

    Journal of Cell Science   130 ( 9 )   1559 - 1569   2017

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    DOI： 10.1242/jcs.196907

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  • Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model Reviewed

    Ono, M., Oshima, M., Ogawa, M., Sonoyama, W., Satoshi Hara, E., Oida, Y., Shinkawa, S., Nakajima, R., Mine, A., Hayano, S., Fukumoto, S., Kasugai, S., Yamaguchi, A., Tsuji, T., Kuboki, T.

    Scientific Reports   7   44522 - 44522   2017

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    DOI： 10.1038/srep44522

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  • MSCs feeder layers induce SMG selforganization and branching morphogenesis Reviewed

    Farahat, M., Sathi, G.A., Hara, E.S., Taketa, H., Kuboki, T., Matsumoto, T.

    PLoS ONE   12 ( 4 )   e0176453   2017

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  • 皮膚創傷治癒過程におけるCCN4/WISP-1の役割

    大野 充昭, 正木 明日香, 前田 あずさ, Hara Emilio S., 小盛 大志, 久保田 聡, Young Marian F., 大橋 俊孝, 窪木 拓男

    日本結合組織学会学術大会プログラム・抄録集   48回   88 - 88   2016.6

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  • Assessment of CCN2 Independent Modules Regenerative Capacity on Osteoarthritis and Further Selecting the Most Suitable Among them as a Potential Therapeutic Drug Reviewed

    Tarek Abdelkader, Eriko Aoyama, Takashi Nishida, Takako Hattori, Danilo Janune, Emilio S. Hara, Mitsuaki Ono, Yasuhiko Tabata, Takuo Kuboki, Satoshi Kubota, Masaharu Takigawa

    FASEB JOURNAL   30   2016.4

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  • Sleep bruxism frequency and platelet serotonin transporter activities in young adult subjects Reviewed

    Minakuchi, H., Sogawa, C., Miki, H., Hara, E.S., Maekawa, K., Sogawa, N., Kitayama, S., Matsuka, Y., Clark, G.T., Kuboki, T.

    Sleep and Breathing   20 ( 1 )   271 - 276   2016.3

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  • Sleep bruxism frequency and platelet serotonin transporter activities in young adult subjects Reviewed

    Hajime Minakuchi, Chiharu Sogawa, Haruna Miki, Emilio S. Hara, Kenji Maekawa, Norio Sogawa, Shigeo Kitayama, Yoshizo Matsuka, Glenn Thomas Clark, Takuo Kuboki

    SLEEP AND BREATHING   20 ( 1 )   271 - 276   2016.3

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  • Antagonistic Effects of Insulin and TGF-β3 during Chondrogenic Differentiation of Human BMSCs under a Minimal Amount of Factors Reviewed

    Emilio Satoshi Hara, Mitsuaki Ono, Yuya Yoshioka, Junji Ueda, Yuri Hazehara, Hai Thanh Pham, Takuya Matsumoto, Takuo Kuboki

    Cells Tissues Organs   201 ( 2 )   88 - 96   2016

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  • CCN4/WISP-1 positively regulates chondrogenesis by controlling TGF-β3 function Reviewed

    Yoshioka, Y., Ono, M., Maeda, A., Kilts, T.M., Hara, E.S., Khattab, H., Ueda, J., Aoyama, E., Oohashi, T., Takigawa, M., Young, M.F., Kuboki, T.

    Bone   83   162 - 170   2016

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  • Fluocinolone acetonideとTGF-β3を用いた強力な軟骨再生(Potent cartilage regeneration with fluocinolone acetonide and TGF-β3)

    Hara Emilio Satoshi, 大野 充昭, Pham Hai Thanh, 久保田 聡, 滝川 正春, Young Marian F., Olsen Bjorn R., 松本 卓也, 窪木 拓男

    日本バイオマテリアル学会大会予稿集   37回   209 - 209   2015.11

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  • CCN4はTGF-β3の機能を制御することで軟骨細胞分化を正に制御する

    吉岡 裕也, 大野 充昭, 前田 あずさ, Hara Emilio Satoshi, Young Marian, 窪木 拓男

    日本骨代謝学会学術集会プログラム抄録集   33回   216 - 216   2015.7

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  • 糖質コルチコイドの中でfluocinolone acetonideはTGF-β3介在性BMSCの軟骨形成の活性化と関節の軟骨修復を促進において特異的な作用を有する(Among glucocorticoids, fluocinolone acetonide is unique in potentiating TGF-β 3-mediated chondrogenesis of BMSCs and promoting articular cartilage repair)

    Hara Emilio Satoshi, 大野 充昭, Pham Hai Thanh, Young Marian F., 久保田 聡, 滝川 正春, 窪木 拓男

    日本骨代謝学会学術集会プログラム抄録集   33回   161 - 161   2015.7

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  • A longitudinal retrospective study of the analysis of the risk factors of implant failure by the application of generalized estimating equations Reviewed

    Noda, K., Arakawa, H., Kimura-Ono, A., Yamazaki, S., Hara, E.S., Sonoyama, W., Maekawa, K., Okura, K., Shintani, A., Matsuka, Y., Kuboki, T.

    Journal of Prosthodontic Research   59 ( 3 )   178 - 184   2015

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  • In silico comparison of the reproducibility of full-arch implant provisional restorations to final restoration between a 3D Scan/CAD/CAM technique and the conventional method Reviewed

    Mino, T., Maekawa, K., Ueda, A., Higuchi, S., Sejima, J., Takeuchi, T., Hara, E.S., Kimura-Ono, A., Sonoyama, W., Kuboki, T.

    Journal of Prosthodontic Research   59 ( 2 )   152 - 158   2015

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  • OstemiR: A Novel Panel of MicroRNA Biomarkers in Osteoblastic and Osteocytic Differentiation from Mesencymal Stem Cells Reviewed

    Eguchi, Takanori, Hara, Emilio Satoshi, Ono, Mitsuaki, Watanabe, Ken, Kuboki, Takuo, Calderwood, Stuart

    Faseb Journal   29   2015

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  • A risk factor analysis of accumulated postoperative pain and swelling sensation after dental implant surgery using a cellular phone-based real-time assessment Reviewed

    Kuroi, R., Minakuchi, H., Hara, E.S., Kawakami, A., Maekawa, K., Okada, H., Kuboki, T.

    Journal of Prosthodontic Research   59 ( 3 )   194 - 198   2015

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  • 炎症環境による歯髄細胞の幹細胞化 歯髄細胞分化に与えるTNF-αの影響

    上枝 麻友, 藤澤 拓生, 大野 充昭, Hara Emilio Satoshi, Pham Thanh Hai, 園山 亘, 窪木 拓男, 松香 芳三

    日本再生歯科医学会誌   12 ( 1 )   48 - 48   2014.12

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  • 出生後のイヌ永久歯胚組織を用いた器官原基法による完全な臓器としての歯の再生

    大野 充昭, 大島 正充, 園山 亘, 小川 美帆, 笈田 育尚, Hara Emilio S., 新川 重彦, 中島 隆, 辻 孝, 窪木 拓男

    日本補綴歯科学会誌   6 ( 特別号 )   103 - 103   2014.5

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  • A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells Reviewed

    Mayu Ueda, Takuo Fujisawa, Mitsuaki Ono, Emilio Satoshi Hara, Hai Thanh Pham, Ryu Nakajima, Wataru Sonoyama, Takuo Kuboki

    Stem Cell Research & Therapy   5 ( 1 )   2014.3

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    DOI： 10.1186/scrt420

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    Other Link： https://link.springer.com/article/10.1186/scrt420/fulltext.html

  • The regenerative effects of CCN2 independent modules on chondrocytes in vitro and osteoarthritis models in vivo Reviewed

    Tarek Abd El Kader, Satoshi Kubota, Takashi Nishida, Takako Hattori, Eriko Aoyama, Danilo Janune, Emilio S. Hara, Mitsuaki Ono, Yasuhiko Tabata, Takuo Kuboki, Masaharu Takigawa

    Bone   59   180 - 188   2014.2

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    DOI： 10.1016/j.bone.2013.11.010

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  • Efficient bone formation in a swine socket lift model using escherichia coli-derived recombinant human bone morphogenetic protein-2 adsorbed in β-tricalcium phosphate Reviewed

    Ono, M., Sonoyama, W., Yamamoto, K., Oida, Y., Akiyama, K., Shinkawa, S., Nakajima, R., Pham, H.T., Hara, E.S., Kuboki, T.

    Cells Tissues Organs   199 ( 4 )   249 - 255   2014

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    DOI： 10.1159/000369061

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  • Mesenchymal stem/progenitor cell isolation from tooth extraction sockets Reviewed

    Nakajima, R., Ono, M., Hara, E.S., Oida, Y., Shinkawa, S., Pham, H.T., Akiyama, K., Sonoyama, W., Maekawa, K., Kuboki, T.

    Journal of Dental Research   93 ( 11 )   1133 - 1140   2014

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    DOI： 10.1177/0022034514549377

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  • miRNA-720 regulates the stem cell phenotype and differentiation of human dental pulp-derived mesenchymal stromal cells Reviewed

    Emilio Satoshi Hara, Mitsuaki Ono, Takanori Eguchi, Hai Thanh Pham, Shoji Tajima, Stuart K. Calderwood, Takuya Matsumoto, Takuo Kuboki

    2014 INTERNATIONAL SYMPOSIUM ON MICRO-NANOMECHATRONICS AND HUMAN SCIENCE (MHS)   2014

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    DOI： 10.1109/MHS.2014.7006080

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    Other Link： http://orcid.org/0000-0001-7374-3487

  • Regeneration of calvarial defects with escherichia coli-derived rhBMP-2 adsorbed in PLGA Membrane Reviewed

    Ono, M., Sonoyama, W., Nema, K., Hara, E.S., Oida, Y., Pham, H.T., Yamamoto, K., Hirota, K., Sugama, K., Sebald, W., Kuboki, T.

    Cells Tissues Organs   198 ( 5 )   367 - 376   2014

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    DOI： 10.1159/000356947

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  • Comparison of platelet serotonin transporter activity in subjects with severe sleep bruxism and control Reviewed

    Minakuchi, H., Sogawa, C., Hara, E.S., Miki, H., Maekawa, K., Sogawa, N., Kitayama, S., Matsuka, Y., Clark, G.T., Kuboki, T.

    Journal of Prosthodontic Research   58 ( 4 )   217 - 222   2014

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    DOI： 10.1016/j.jpor.2014.06.003

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  • Immunotherapy in Transplantation Reviewed

    Akiyama, K., Hara Satoshi, E., Kuboki, T.

    Stem Cell Biology and Tissue Engineering in Dental Sciences   2014

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    DOI： 10.1016/B978-0-12-397157-9.00068-0

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  • 未分化性維持に関与しているmiRNA-720は歯髄細胞の細胞増殖・分化を制御する

    Emilio Hara, 大野 充昭, Hai Pham, 窪木 拓男

    Journal of Oral Biosciences Supplement   2013   155 - 155   2013.9

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  • 抜歯窩肉芽組織からの新規間葉系幹細胞の同定

    中島 隆, 大野 充昭, 園山 亘, 笈田 育尚, Hara Emilio S., 前川 賢治, 窪木 拓男

    日本補綴歯科学会誌   5 ( 特別号 )   112 - 112   2013.5

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  • 皮膚創傷治癒過程におけるCCN4/WISP-1遺伝子の役割

    正木 明日香, 大野 充昭, 園山 亘, Hara Emilio S., 前田 あずさ, Young Marian F., 窪木 拓男

    日本補綴歯科学会誌   5 ( 特別号 )   227 - 227   2013.5

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  • A novel vibratory stimulation-based occlusal splint for alleviation of TMD painful symptoms: A pilot study Reviewed

    Hara, E.S., Witzel, A.L., de Luca, C.E.P., Ballester, R.Y., Kuboki, T., Bolzan, M.C.

    Journal of Oral Rehabilitation   40 ( 3 )   179 - 184   2013.3

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    DOI： 10.1111/joor.12026

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  • A novel vibratory stimulation-based splint for chronic and untreatable masticatory myofascial pain: A case-series Reviewed

    Hara, E.S., Witzel, A.L., de Luca, C.E.P., Ballester, R.Y., Bolzan, M.C.

    Journal of Prosthodontic Research   57 ( 1 )   62 - 66   2013.1

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    DOI： 10.1016/j.jpor.2012.08.005

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  • A retrospective comparative 8-year study of cumulative complications in teeth adjacent to both natural and implant-supported fixed partial dentures Reviewed

    Yamazaki, S., Arakawa, H., Maekawa, K., Noda, K., Hara, E.S., Minakuchi, H., Sonoyama, W., Matsuka, Y., Kuboki, T.

    International Journal of Prosthodontics   26 ( 3 )   260 - 264   2013

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.11607/ijp.3120

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  • OstemiR: A Novel Panel of MicroRNA Biomarkers in Osteoblastic and Osteocytic Differentiation from Mesencymal Stem Cells Reviewed

    Eguchi, T., Watanabe, K., Hara, E.S., Ono, M., Kuboki, T., Calderwood, S.K.

    PLoS ONE   8 ( 3 )   2013

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    DOI： 10.1371/journal.pone.0058796

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  • A retrospective comparative ten-year study of cumulative survival rates of remaining teeth in large edentulism treated with implant-supported fixed partial dentures or removable partial dentures Reviewed

    Yamazaki, S., Arakawa, H., Maekawa, K., Hara, E.S., Noda, K., Minakuchi, H., Sonoyama, W., Matsuka, Y., Kuboki, T.

    Journal of Prosthodontic Research   57 ( 3 )   156 - 161   2013

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    DOI： 10.1016/j.jpor.2013.03.003

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  • Identification of risk factors for fracture of veneering materials and screw loosening of implant-supported fixed partial dentures in partially edentulous cases Reviewed

    Noda, K., Arakawa, H., Maekawa, K., Hara, E.S., Yamazaki, S., Kimura-Ono, A., Sonoyama, W., Minakuchi, H., Matsuka, Y., Kuboki, T.

    Journal of Oral Rehabilitation   40 ( 3 )   214 - 220   2013

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    DOI： 10.1111/joor.12029

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  • MiRNA-720 controls stem cell phenotype, proliferation and differentiation of human dental pulp cells Reviewed

    Hara, E.S., Ono, M., Eguchi, T., Kubota, S., Pham, H.T., Sonoyama, W., Tajima, S., Takigawa, M., Stuart K, C., Kuboki, T.

    PLoS ONE   8 ( 12 )   2013

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    DOI： 10.1371/journal.pone.0083545

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  • Retrospective investigation of the remaining teeth status of patients with implant-supported fixed partial dentures in unilateral free-end edentulism Reviewed

    Yamazaki, S., Arakawa, H., Maekawa, K., Hara, E.S., Noda, K., Minakuchi, H., Sonoyama, W., Matsuka, Y., Kuboki, T.

    Journal of Prosthodontic Research   57 ( 4 )   262 - 267   2013

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    Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.jpor.2013.08.001

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  • Multiple sleep bruxism data collected using a self-contained EMG detector/analyzer system in asymptomatic healthy subjects Reviewed

    Hajime Minakuchi, Chiyomi Sakaguchi, Emilio S. Hara, Kenji Maekawa, Yoshizo Matsuka, Glenn T. Clark, Takuo Kuboki

    Sleep and Breathing   16 ( 4 )   1069 - 1072   2012.12

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    DOI： 10.1007/s11325-011-0602-1

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    Other Link： http://link.springer.com/article/10.1007/s11325-011-0602-1/fulltext.html

  • Matrix metalloproteinase-8 is the major potential collagenase in active peri-implantitis Reviewed

    Hikaru Arakawa, Junji Uehara, Emilio Satoshi Hara, Wataru Sonoyama, Aya Kimura, Manabu Kanyama, Yoshizo Matsuka, Takuo Kuboki

    Journal of Prosthodontic Research   56 ( 4 )   249 - 255   2012.10

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    DOI： 10.1016/j.jpor.2012.07.002

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  • Occlusal dysesthesia: A qualitative systematic review of the epidemiology, aetiology and management Reviewed

    Hara, E.S., Matsuka, Y., Minakuchi, H., Clark, G.T., Kuboki, T.

    Journal of Oral Rehabilitation   39 ( 8 )   630 - 638   2012.8

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    DOI： 10.1111/j.1365-2842.2012.02300.x

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  • 大腸菌由来BMP-2を応用した骨再生療法の開発と評価

    園山 亘, 大野 充昭, 笈田 育尚, Hara Emilio Satoshi, 新川 重彦, 中島 隆, 正木 明日香, 松香 芳三, 山本 克史, 広田 一男, 洲鎌 和茂, 窪木 拓男

    日本歯科医師会雑誌   65 ( 5 )   678 - 678   2012.8

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  • 睡眠時ブラキシズム頻度と末梢セロトニントランスポーター輸送能との関連

    水口 一, 三木 春奈, 十川 千春, Hara Emilio Satoshi, 藤澤 拓生, 前川 賢治, 松香 芳三, 十川 紀夫, 北山 滋雄, 窪木 拓男

    日本補綴歯科学会誌   4 ( 特別号 )   213 - 213   2012.5

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  • Response shift in oral health-related quality of life measurement in patients with partial edentulism Reviewed

    Kimura, A., Arakawa, H., Noda, K., Yamazaki, S., Hara, E.S., Mino, T., Matsuka, Y., Mulligan, R., Kuboki, T.

    Journal of Oral Rehabilitation   39 ( 1 )   44 - 54   2012.1

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    DOI： 10.1111/j.1365-2842.2011.02241.x

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  • A problem-based learning tutorial for dental students regarding elderly residents in a nursing home in Japan Reviewed

    Matsuka, Y., Nakajima, R., Miki, H., Kimura, A., Kanyama, M., Minakuchi, H., Shinkawa, S., Takiuchi, H., Nawachi, K., Maekawa, K., Arakawa, H., Fujisawa, T., Sonoyama, W., Mine, A., Hara, E.S., Kikutani, T., Kuboki, T.

    Journal of Dental Education   76 ( 12 )   1580 - 1588   2012

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  • The association between oral health-related quality of life and self-rated presenteeism Reviewed

    Takiuchi, Hiroya, Kimura-Ono, Aya, Arakawa, Hikaru, Mino, Takuya, Masaki, Asuka, Hara, Emilio Satoshi, Kanyama, Manabu, Matsuka, Yoshizo, Kuboki, Takuo

    Quality of Life Research   21   71 - 72   2012

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  • 睡眠時ブラキシズム発症頻度と末梢セロトニントランスポーター機能

    水口 一, ハラエミリオ, 三木 春奈, 藤澤 拓生, 前川 賢治, 松香 芳三, 窪木 拓男

    日本顎関節学会雑誌   23 ( Suppl. )   115 - 115   2011.7

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  • RELATIONSHIP BETWEEN SLEEP BRUXISM FREQUENCY AND UPTAKE ABILITY OF HUMAN PERIPHERAL SEROTONIN TRANSPORTER

    Minakuchi, H., Hara, E. S., Sogawa, C., Miki, H., Fujisawa, T., Maekawa, K., Matsuka, Y., Sogawa, N., Kitayama, S., Kuboki, T.

    Sleep   34   2011

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  • A 15-year clinical comparative study of the cumulative survival rate of cast metal core and resin core restorations luted with adhesive resin cement Reviewed

    Hikasa, T., Matsuka, Y., Mine, A., Minakuchi, H., Hara, E.S., Van Meerbeek, B., Yatani, H., Kuboki, T.

    International Journal of Prosthodontics   23 ( 5 )   397 - 405   2010

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  • Influence of unilateral posterior disocclusion on the body balance of rats Reviewed International journal

    REVISTA DE ODONTOLOGIA DA UNICID   2008

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Books

MISC

  • Novel function of BMP-2 in inhibiting bone formation in marrow environment

    Ha Nguyen Thi, Mitsuaki Ono, Yasutaka Oida, Emilio Satoshi Hara, Taishi Komori, Kentaro Akiyama, Ha Nguyen Thi Thu, Hai Thanh Pham, Kyawthu Aung, Toshitaka Oohashi, Takuo Kuboki

    JOURNAL OF BONE AND MINERAL RESEARCH   33   338 - 338   2018.11

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  • Regenerative Medicine Reasearch with Bite

    Ono M, Hara ES, Kuboki T

    Nature/Nature Index 2017 Japan   543 ( 7645 )   S32-S32   2017

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  • Assessment of CCN2 Independent Modules Regenerative Capacity on Osteoarthritis and Further Selecting the Most Suitable Among them as a Potential Therapeutic Drug

    Tarek Abdelkader, Eriko Aoyama, Takashi Nishida, Takako Hattori, Danilo Janune, Emilio S. Hara, Mitsuaki Ono, Yasuhiko Tabata, Takuo Kuboki, Satoshi Kubota, Masaharu Takigawa

    FASEB JOURNAL   30   2016.4

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  • フルオシノロンアセトニドは関節軟骨再生におけるTGF-β3誘導性軟骨細胞分化を相乗的に促進する

    HARA Emilio Satoshi, HARA Emilio Satoshi, 大野充昭, PHAM Hai Thanh, 園山亘, 久保田聡, 滝川正春, 松本卓也, YOUNG Marian F., OLSEN Bjorn R., 窪木拓男

    日本軟骨代謝学会プログラム・抄録集   29th   2016

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  • 関節軟骨治癒におけるCCN4/WISP-1遺伝子の役割

    吉岡裕也, 大野充明, 前田あずさ, HARA Emilio S., 秋山謙太郎, 園山亘, YOUNG Marian F., 窪木拓男

    日本軟骨代謝学会プログラム・抄録集   28th   2015

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  • 軟骨分化におけるCCN4/WISP-1の機能的解析

    吉岡裕也, 大野充昭, 前田あずさ, HARA Emilio S, 秋山謙太郎, 園山亘, YOUNG Marian F, 窪木拓男

    日本軟骨代謝学会プログラム・抄録集   27th   2014

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  • グルココルチコイド薬フルオシノロンアセトニドはAKT/mTORシグナル経路を介し骨髄由来間葉系間質細胞の軟骨分化を増強する

    HARA Emilio Satoshi, 大野充昭, 久保田聡, 園山亘, PHAM Hai Thanh, 滝川正春, 窪木拓男

    日本軟骨代謝学会プログラム・抄録集   26th   2013

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  • 軟骨分化促進作用を有するグルココルチコイド薬フルオシノロンアセトニド

    HARA Emilio Satoshi, 大野充昭, 久保田聡, 園山亘, 藤澤拓生, 滝川正春, 窪木拓男

    日本軟骨代謝学会プログラム・抄録集   25th   2012

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Presentations

  • Quantum chemical analysis of the hydrolysis reactions of different types of phospholipids

    Cheng Y, Hara ES, Kunioshi N

    2024.3.19 

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Awards

  • 日本バイオマテリアル学会 研究奨励賞

    2019.6  

    ハラ エミリオ サトシ

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  • 学会賞

    2016.2   日本軟骨代謝学会  

    ハラ エミリオ サトシ

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  • Hatton Divisional Award

    2012.6   IADR  

    Hara Emilio Satoshi

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  • 岡山大学大学院医歯薬学総合研究科 教育功労者受賞

    2022.1  

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  • 日本歯科理工学会 株式会社ジーシー賞

    2019.4  

    ハラ エミリオ サトシ

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  • 研究奨励賞

    2018.4   日本歯科理工学会  

    ハラ エミリオ サトシ

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  • 優秀発表賞

    2016.2   日本バイオマテリアル学会中四国ブロック  

    ハラ エミリオ サトシ

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  • 優秀発表賞

    2015.7   超高速バイオアセンブラ  

    ハラ エミリオ サトシ

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  • Young Investigator Award

    2012.12   Japanese Association for Dental Research  

    Hara Emilio Satoshi

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  • 優秀発表賞受賞

    2011.7   日本骨代謝学会学  

    ハラ エミリオ サトシ

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Research Projects

  • 細胞膜を基盤材料とした生体組織の修復技術の開発研究

    Grant number：JPMJFR210X  2022.04 - 2025.03

    Japan Science and Technology Agency  Fusion Oriented Research for Disruptive Science and Technology 

    ハラ エミリオ・サトシ

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  • Towards the understanding and designing of a bioinspired hematopoietic stem cell niche microenvironment

    Grant number：20KK0368  2021 - 2024

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))  Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))

    ハラ エミリオ・サトシ

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    Grant amount：\14040000 （ Direct expense: \10800000 、 Indirect expense：\3240000 ）

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  • Physiologically-Integrated Wearable Devices with Mind-Body Practice for Stress Management

    Grant number：20335922  2020.11 - 2021.03

    国立研究開発法人日本医療研究開発機構（AMED）/ The New York Academy of Sciences  Interstellar Initiative（医療分野国際科学技術共同研究開発推進事業） 

    ハラ エミリオ・サトシ

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  • Reproduction and control of the initial steps of bone marrow formation by using cell membrane nanofragments

    Grant number：20H04534  2020.04 - 2024.03

    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)

    ハラ エミリオ・サトシ, 松本 卓也, 大野 充昭, 長岡 紀幸, 岡田 正弘, 藤枝 俊宣

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    Authorship：Principal investigator 

    Grant amount：\17810000 （ Direct expense: \13700000 、 Indirect expense：\4110000 ）

    骨髄形成のメカニズムを解明することは、in vitroにて生体を模倣した骨髄組織を構築することが可能となり、骨-造血疾患のドラッグスクリーニングや再生治療の技術開発への新たな展開に繋がることが期待されるが、未だ達成されていない。我々はこれまでに、「細胞膜ナノフラグメント」が海綿骨形成に重要な役割を果たすことを発表した。また、海綿骨形成後に、間葉系幹細胞などの細胞が海綿骨の表面に定着し、骨髄を形成することが明らかとなった。つまり、「細胞膜ナノフラグメント」は海綿骨・骨髄初期形成に関与していることが示唆された。さらに、培養細胞から細胞膜ナノフラグメントを単離する手法を確立し、この細胞膜ナノフラグメントを用いることで、in vitroにて海綿骨形成を迅速に誘導することに成功した。
    本研究では、海綿骨-骨髄形成過程について、生物学・材料科学的に解析する。また、リバースエンジニアリング的に骨髄初期形成過程をin vitroで模倣・構築し、その制御を試みる。そして、骨髄初期の構造と機能を精密に再現することで、細胞膜ナノフラグメントを基盤とした骨髄の初期形成メカニズムを再検討し、より深い理解を目指す。
    本年度は以下の実験を実施した。
    １）新生児マウス大腿骨骨端部における海綿骨の初期形成時期（生後6日目）から骨髄初期形成時期（生後12日目）の組織変化を組織学的・材料学的に解析した。また、骨髄初期の三次元的情報を得る為、新生児マウス大腿骨骨端部の骨髄初期形成時期を集束イオンビーム・走査型電子顕微鏡（FIB-SEM）を用いの三次元観察を行うための準備を行った。
    ２）骨髄初期形成に関与する細胞集団の遺伝子発現パターンを次世代シーケンサーを用いて解析を行った。これらの解析により、海綿骨の形態変化、ならびに海綿骨に定着し、骨髄を形成する細胞集団の遺伝子発現パターンなどの特徴を明らかにすることが期待できる。

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  • Development of a novel osteoinductive material using cell membrane nanofragments

    Grant number：18K17119  2018.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists  Grant-in-Aid for Early-Career Scientists

    Hara Emilio Satoshi

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    Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）

    We have previously analyzed the early process of bone formation in vivo, in mouse femur epiphysis. Interestingly, we found that cell (plasma) membrane nanofragments (PMNFs) were the nucleation site for bone formation. Moreover, isolation of PMNFs from cultured cells induced mineralization in just 2 days.
    This study was conducted to evaluate the ability of PMNFs to promote fast bone repair. For that purpose, this study aimed at establishing a method for fabrication of PMNFs and optimizing the method for using PMNFs in bone regeneration. The results showed that pre-conditioned PMNFs can promote rapid bone repair of mouse calvaria.

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  • Analysis of the initial mineralization in secondary ossification center by the Life Science and Material Science viewpoints

    Grant number：16H06990  2016.08 - 2018.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up  Grant-in-Aid for Research Activity Start-up

    Hara Emilio Satoshi, Matsumoto Takuya, Okada Masahiro, Kuboki Takuo, Nagaoka Noriyuki, Hattori Takako

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    Grant amount：\2860000 （ Direct expense: \2200000 、 Indirect expense：\660000 ）

    We investigated the initial stages of endochondral ossification during secondary ossification of mouse femur epiphysis from the Life Science and Material Science viewpoints. We found that the very initial starting point of mineral formation in the epiphysis occurs at post-natal day 6 (P6).
    Electron microscopy-based ultrastructural analysis showed that cell-secreted matrix vesicles were absent in the early steps of osteoblast-independent endochondral ossification. Instead, chondrocyte membrane fragments were found in the fibrous matrix surrounding the hypertrophic chondrocytes. EDS analysis and electron diffraction study indicated that cell membrane fragments acted as nuclei for newly formed calcospherites which initially showed an amorphous calcium phosphate phase, and then transformed into apatite crystal phase. These findings would be valuable to develop novel organic-inorganic hybrid materials for manipulation of biomineralization.

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  • Creation of cell membrane-mimicking biomaterials and application to rapid bone regeneration

    Grant number：22H03274  2022.04 - 2026.03

    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)

    松本 卓也

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    Grant amount：\17420000 （ Direct expense: \13400000 、 Indirect expense：\4020000 ）

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  • In vitro creation of bone marrow-like tissue by introducing vascular network into organoids

    Grant number：22H03952  2022.04 - 2025.03

    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)

    佐々木 淳一

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    Grant amount：\17290000 （ Direct expense: \13300000 、 Indirect expense：\3990000 ）

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  • Analysis and control of interface between soft tissue and hard adhesive

    Grant number：21H03123  2021.04 - 2024.03

    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)

    岡田 正弘, 柴田 陽, 松本 卓也, ハラ エミリオ・サトシ

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    Authorship：Coinvestigator(s) 

    Grant amount：\17290000 （ Direct expense: \13300000 、 Indirect expense：\3990000 ）

    我々は、医療材料として用いられる無機材料（チタンやアパタイト）に適切な表面構造を構築することで、ハイドロゲル（生体軟組織や合成ゲル）がその無機材料と瞬時に強く接着することを見出した。本研究課題では、これら無機系固体接着材とハイドロゲルの接着現象を界面科学的観点から解析する。具体的には、まず、条件を変化させて作製した固体接着材表面の化学的・物理的性質を評価する。また、各種官能基を導入した粘弾性特性の異なるハイドロゲルを作製し、固体接着材とハイドロゲルの接着強さを評価する。この際、生体内における接着安定性についても評価を行う。さらに、各種分析法を用いて固体接着材とハイドロゲル間の界面における相互作用についての情報を収集する。以上の情報を総合し、ソフト（ハイドロゲル）とハード（無機系固体接着材）間の接着現象を理解することを目的とする。
    上記の目的を達成するために本年度の検討では、まず、条件を変化させて無機系固体接着材を作製してその表面性状を評価した。無機系固体接着材としてのアパタイトは湿式法によって合成し、疎水性モールドにキャスト後に焼成することでナノ多孔質体として作製した。この際の焼成条件によってアパタイトの表面性状を変化させた。チタンは薄膜状のものを準備し、酸処理によって表面処理した。これら無機材料の表面性状は、化学的観点（組成、結晶性）および物理的観点（表面粗さ、弾性率）から評価を行った。具体的には、表面形態を電子顕微鏡観察および表面粗さから評価した。また、X線回折法を用いて結晶構造を評価した。次に、組成の異なるハイドロゲルを作製し、表面性状の異なる無機材料とハイドロゲルを組み合わせて接着試験を行い、ハイドロゲルと無機系固体接着材間の接着性を定量的に評価した。以上の検討結果を取りまとめて学会発表ならびに論文発表を行った。

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  • Designing of novel bone-inducing molecules by an experimental-computational approach

    Grant number：21K09963  2021.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    国吉 ニルソン, ハラ エミリオ・サトシ

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    Authorship：Coinvestigator(s) 

    Grant amount：\3900000 （ Direct expense: \3000000 、 Indirect expense：\900000 ）

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  • リン脂質石灰化のバイオマテリアルズインフォマティクス解析

    2020.06 - 2021.03

    令和元年度（2020）早稲田大学 各務記念材料技術研究所 共同研究 

    ハラ エミリオ・サトシ, 国吉 ニルソン

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    Authorship：Principal investigator 

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  • 骨メカノトランスダクションおよび組織工学用の生体機能性電気活性ポリマーの開発

    2020.04 - 2022.03

    二国間交流事業 共同研究 

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    Authorship：Coinvestigator(s) 

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  • 間葉系幹細胞制御技術を指向した生体模倣骨組織バイオデバイスの創製

    2020.04 - 2021.03

    公益財団法人 池谷科学技術振興財団 

    ハラ エミリオ・サトシ

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    Authorship：Principal investigator 

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  • 新規骨形成誘導材料の開発を指向したリン脂質石灰化のin vitro実験およびシミュレーションによる反応機構解析

    2020.04 - 2021.03

    三菱マテリアル株式会社―早稲田大学理工学術院包括協定 

    国吉 ニルソン, ハラ エミリオ・サトシ

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    Authorship：Coinvestigator(s) 

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  • リン脂質石灰化のバイオマテリアルズインフォマティクス解析

    2019.06 - 2020.03

    令和元年度（2019）早稲田大学 各務記念材料技術研究所 共同研究 

    ハラ エミリオ・サトシ、国吉ニルソン

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    Authorship：Principal investigator 

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  • 基底膜構成分子の誘導制御による低侵襲角化歯肉獲得療法の確立

    Grant number：19H03841  2019.04 - 2023.03

    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)

    前川 賢治, 窪木 拓男, 冨田 秀太, ハラ エミリオ・サトシ, 大橋 俊孝, 大野 充昭

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    Authorship：Coinvestigator(s) 

    Grant amount：\17030000 （ Direct expense: \13100000 、 Indirect expense：\3930000 ）

    基底膜直下に存在する角化歯肉由来間葉細胞と非角化歯肉由来間葉細胞の遺伝子発現の相違を明らかにすることで，上皮細胞の角化に関わっている間葉細胞からのシグナル分子を抽出することが可能であると考える。そこで，令和元年度は，レーザーマイクロダイセクション法とRNA-Seq を組み合わせた候補因子の抽出を目的に，以下の実験を実施してきた。
    間葉組織は，筋肉や脂肪など様々な組織を含むことから，マクロレベルで口蓋粘膜から間葉組織を採取すると，様々な組織を含んでしまう。基底膜直下の間葉組織の遺伝子発現解析を正確にするには，特異的に組織を採取することが可能なレーザーマイクロダイセクション法を用いる必要がある。そこで，マウスの口蓋粘膜（角化粘膜）と頬粘膜（非角化粘膜）の凍結組織切片を作製し，サンプルの厚み，固定方法，染色方法，レーザーの強度の調整等，様々な条件検討を行い，本組織において最適な条件を見出した。そして，これらのサンプルからRNAを抽出し，RNA-seqが可能な質の高いRNAが回収できていることを，TapStation (アジレント)にて確認した。
    また、in vitroにおいて，角化粘膜の間葉組織に高発現している遺伝子をRNA-seq解析から抽出後，さらなる候補因子の絞り込みをin vitroにて行う予定である。そこで，令和元年度は，ヒト口腔扁平上皮癌由来の口腔粘膜上皮細胞であるTR146と，ヒト口腔粘膜細胞由来線維芽細胞を用いた三次元共培養実験モデルを構築すべく，コラーゲンゲルの種類，濃度や細胞の濃度などの条件検討を行い，正常な口腔粘膜組織に類似したin vitro モデル構築に適正な条件の絞り込みを終えた。

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  • The clarification of bone formation and absorption mechanism in the bone marrow microenvironment

    Grant number：19H03842  2019.04 - 2022.03

    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)

    Ono Mitsuaki

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    Authorship：Coinvestigator(s) 

    Grant amount：\17550000 （ Direct expense: \13500000 、 Indirect expense：\4050000 ）

    BMP-2 has been widely studied for its potent ability to induce osteoblast differentiation and ectopic bone formation, and is already in clinical use worldwide. On the other hand, we have shown that BMP-2 inhibits bone formation in the bone marrow. However, the mechanism by which BMP-2 suppresses bone formation remains unclear. Therefore, we analyzed the detail of BMP-2 induced bone. Single cell RNA-seq analysis revealed that BMP-2-induced bone formed bone marrow with hematopoietic function. These results suggest that BMP-2 has the ability to regenerate bone marrow as an organ, and may suppress bone formation in the bone marrow in order to reserve space for hematopoiesis.

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  • 材料化学実験および反応計算によるリン酸カルシウム材料の形成機構の解析

    2019.04 - 2020.03

    三菱マテリアル株式会社―早稲田大学理工学術院包括協定 

    国吉 ニルソン, ハラ エミリオ・サトシ

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    Authorship：Coinvestigator(s) 

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  • The functional analysis of WISP1 gene aimed at the prevention of osteoarthritis

    Grant number：18K09682  2018.04 - 2021.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Maeda Azusa

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    Authorship：Coinvestigator(s) 

    Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）

    The purpose of this study was to elucidate the relationship between WISP1 gene and osteoarthritis (OA). In this study, we found that severity of OA mouse models in the Wisp1 deficient (Wisp1-KO) mouse was milder compared to wild type mouse. We also found that expression level of genes related to the extracellular matrix degrading proteases in the Wisp1-KO-OA knee joint tissue was lower compared to wildtype, it is suggesting that WISP1 is involved in pathogenic mechanism and progress of OA by promoting the secretion of ECM-degrading proteases.

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  • Understanding of molecular&#160;mechanisms&#160;of&#160;tooth development using iPS interference and application to tooth regeneration techniques

    Grant number：18H02991  2018.04 - 2021.03

    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)

    Kuboki Takuo

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    Authorship：Coinvestigator(s) 

    Grant amount：\17550000 （ Direct expense: \13500000 、 Indirect expense：\4050000 ）

    Whole-tooth regeneration is ultimate goal in dental field and the goal of this study is to identify the master transcription factors that characterize tooth germ derived epithelial and mesenchymal cells and develop method to generate those cells. First, we analyzed the mouse embryonic tooth germ and human stem cell from the apical papilla (hSCAP) by RNA-Seq and performed iPS interference to identify the potential transcription factors. Finally, candidate transcription factors were overexpressed in human adult dermal fibroblast (hADF), resulting that hADF was induced into the cells similar to tooth germ derived mesenchymal cells.

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  • 三次元骨組織迅速作製技術の構築を指向したリン脂質ナノフラグメント作製法の確立

    2018.04 - 2019.03

    公益財団法人京都技術科学センター 

    ハラ エミリオ・サトシ

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    Authorship：Principal investigator 

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  • Bioengineering bridges between Okayama and Sao Paulo Universities

    2017

    岡山大学  H29岡山大学次世代研究コア形成支援事業・若手研究者育成支援事業 

    ハラ エミリオ・サトシ

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    Authorship：Principal investigator 

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  • 合成微小環境を用いた軟骨組織のｉｎ ｖｉｔｒｏ構築

    Grant number：14F04106  2014.04 - 2016.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS Fellows  Grant-in-Aid for JSPS Fellows

    松本 卓也, ハラ エミリオ・サトシ

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    Grant amount：\2400000 （ Direct expense: \2400000 ）

    The purpose of this study was to identify new methods and culture conditions to enhance chondrogenic differentiation of human bone marrow-derived mesenchymal stem/progenitor cells (hBMSCs) by applying chemical, physical and biological cues, including overexpression of DNA methyltransferases (DNMTs) in cells. We attempted to fabricate a chemically- and physically-controlled microenvironment using materials (e.g., hydrogels) that recapitulate native cell niche characteristics to optimally modulate the chondrogenic differentiation of BMSCs. Besides the physical and chemical stimulations, we also evaluated the chondrogenic differentiation of hBMSCs after overexpression of DNMTs that eventually induce DNA methylation at CPG rich regions of key genes. To study the effect of DNMTs on chondrogenesis of hBMSCs, we transfected overexpression vectors of DNMT3A, DNMT3B and the pcDNA control in hBMSCs, and culture the cells in a 3D micromass culture system with growth factors and glucocorticoids.
    Additionally, since in vitro synthesized cartilage tissue generally undergoes through mineralization, we also attempted to understand the mechanisms involved in the chondrocyte death associated with initial mineralization process by using the secondary ossification center of mouse femur as in vivo model.

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  • 生体材料学ＩＩ（講義・演習） （2019academic year） 特別  - その他

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  • 歯科医用工学演習２ （2018academic year） 特別  - その他

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  • 生体材料学実習 （2018academic year） 特別  - その他

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  • 生体材料学１ （2018academic year） 特別  - その他

  • 生体材料学１　 （2018academic year） 特別  - その他

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  • 生体材料学Ｉ（演習・実習） （2018academic year） 特別  - その他

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Social Activities

  • 歯を科学する！（科学キッズフェスティバルin京山祭）

    2022.12.11

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Academic Activities

  • ACS Applied Materials & Interfaces International contribution

    Role(s)：Peer review

    Hara Emilio Satoshi  2022.1 - 2022.12

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    Type：Peer review