Faculty Profiles - HARA EMILIO SATOSHI

Papers - HARA EMILIO SATOSHI

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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

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

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

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

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

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

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

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

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

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

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

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 2025.7

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

DOI： 10.3390/ma14010208

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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

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

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.

DOI： 10.3390/ma13225099

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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

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

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

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

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

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.

DOI： 10.3390/ijms21155327

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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

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

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

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

Authorship：Corresponding author Publishing type：Research paper (scientific journal) Publisher：S. Karger AG

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.

DOI： 10.1159/000502885

PubMed

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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

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

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

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

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.

DOI： 10.1016/j.dental.2019.04.002

PubMed

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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

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

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

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

New Functions of Classical Compounds against Orofacial Inflammatory Lesions Reviewed

Norifumi Moritani, Emilio Hara, Satoshi Kubota

Medicines 5 ( 4 ) 118 - 118 2018.11

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

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.

DOI： 10.3390/medicines5040118

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Immunotherapy in Transplantation Reviewed

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

Stem Cell Biology and Tissue Engineering in Dental Sciences 2014

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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