Faculty Profiles - HARA EMILIO SATOSHI

Papers - HARA EMILIO SATOSHI

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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

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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

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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

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Papers - HARA EMILIO SATOSHI