2021/04/08 更新

写真a

オオノ ミツアキ
大野 充昭
ONO Mitsuaki
所属
医歯薬学域 准教授
職名
准教授
外部リンク

学位

  • 博士 (歯学) ( 岡山大学 )

研究キーワード

  • 骨免疫学

  • 軟骨代謝学

  • 骨代謝学

  • 再生歯学

  • 口腔インプラント学

  • 歯科補綴学

研究分野

  • ライフサイエンス / 口腔再生医学、歯科医用工学

  • ライフサイエンス / 補綴系歯学

学歴

  • 岡山大学大学院医歯薬学総合研究科   大学院 博士課程  

    2003年4月 - 2007年3月

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  • 岡山大学   歯学部 卒業  

    - 2003年3月

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経歴

  • 岡山大学大学院医歯薬学総合研究科   分子医化学分野   准教授

    2019年5月 - 現在

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  • 岡山大学大学院医歯薬学総合研究科   インプラント再生補綴学分野   臨床登録医

    2015年8月 - 現在

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  • 岡山大学大学院医歯薬学総合研究科   分子医化学分野   助教

    2015年8月 - 2019年4月

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  • 岡山大学大学院医歯薬学総合研究科   インプラント再生補綴学分野   助教

    2011年4月 - 2015年7月

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  • 岡山大学大学院医歯薬学総合研究科   インプラント再生補綴学分野   特任助教 (研究)

    2009年10月 - 2011年3月

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  • NIDCR/NIH   Molecular Biology of Bones and Teeth Section, Craniofacial and Skeletal Diseases Branch   Visiting Fellow

    2007年4月 - 2009年9月

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▼全件表示

所属学協会

 

論文

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

    Nomura Y, Hara ES, Yoshioka Y, Nguyen HT, Nosho S, Komori T, Ishibashi K, Oohashi T, Ono M, Kuboki T

    Cells, tissues, organs   1 - 12   2019年10月

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

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

    International Journal of Molecular Sciences20 ( 19 ) 4739 - 4739   2019年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:{MDPI} {AG}  

    DOI: 10.3390/ijms20194739

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  • Postnatal Runx2 deletion leads to low bone mass and adipocyte accumulation in mice bone tissues. 査読 国際誌

    Ikue Tosa, Daisuke Yamada, Misa Yasumatsu, Eiichi Hinoi, Mitsuaki Ono, Toshitaka Oohashi, Takuo Kuboki, Takeshi Takarada

    Biochemical and biophysical research communications516 ( 4 ) 1229 - 1233   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Global gene deletion studies have established that Runt-related transcription factor-2 (Runx2) is essential during skeletogenesis for osteoblastic differentiation in both intramembranous and endochondral ossification processes. However, the postnatal significance of Runx2 in vivo is poorly understood because a global Runx2 deletion causes perinatal lethality. In this study, we generated tamoxifen-induced Runx2 global deficient mice by crossing Runx2flox mice with ROSA26-CreERT2 mice (Rosa26-CreERT2; Runx2flox/flox). Four-week-old mice were intraperitoneally treated with tamoxifen for five consecutive days, sacrificed, and analyzed six weeks after tamoxifen administration. Deletion of Runx2 led to low bone mass, which is associated with decreased bone formation and bone resorption as well as excessive bone marrow adiposity. Collectively, postnatal Runx2 absolutely plays an important role in maintaining the homeostasis of bone tissues not only in bone mass, but also in the bone marrow environment.

    DOI: 10.1016/j.bbrc.2019.07.014

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  • Collagen XVIII Deposition in the Basement Membrane Zone beneath the Newly Forming Epidermis during Wound Healing in Mice. 査読

    Takahiro Maeba, Tomoko Yonezawa, Mitsuaki Ono, Yasuko Tomono, Ritva Heljasvaara, Taina Pihlajaniemi, Kiichi Inagawa, Toshitaka Oohashi

    Acta medica Okayama73 ( 2 ) 135 - 146   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The basement membrane (BM) is composed of various extracellular molecules and regulates tissue regeneration and maintenance. Here, we demonstrate that collagen XVIII was spatiotemporally expressed in the BM during skin wound healing in a mouse excisional wound-splinting model. Re-epithelialization was detected at days 3 and 6 post-wounding. The ultrastructure of epidermal BM was discontinuous at day 3, whereas on day 6 a continuous BM was observed in the region proximal to the wound edge. Immunohistochemistry demonstrated that collagen XVIII was deposited in the BM zone beneath newly forming epidermis in day 3 and 6 wounds. Laminin-332, known to be the earliest BM component appearing in wounds, was colocalized with collagen XVIII in the epidermal BM zone at days 3 and 6. The deposition of α1(IV) collagen and nidogen-1 in the epidermal BM zone occurred later than that of collagen XVIII. We also observed the short isoform of collagen XVIII in the epidermal BM zone at day 3 post-wounding. Collectively, our results suggested that collagen XVIII plays a role in the formation of the dermal-epidermal junction during re-epithelialization, and that it is the short isoform that is involved in the early phase of re-epithelialization.

    DOI: 10.18926/AMO/56649

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

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

    International Journal of Molecular Sciences20 ( 5 )   2019年3月

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3390/ijms20051097

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  • Glutathione accelerates osteoclast differentiation and inflammatory bone destruction. 査読

    Fujita H, Ochi M, Ono M, Aoyama E, Ogino T, Kondo Y, Ohuchi H

    Free radical research53 ( 2 ) 226 - 236   2019年2月

  • Resolvin D2 Induces Resolution of Periapical Inflammation and Promotes Healing of Periapical Lesions in Rat Periapical Periodontitis. 査読

    Siddiqui YD, Omori K, Ito T, Yamashiro K, Nakamura S, Okamoto K, Ono M, Yamamoto T, Van Dyke TE, Takashiba S

    Frontiers in immunology10   307   2019年

  • Inhibition of the glutamine transporter SNAT1 confers neuroprotection in mice by modulating the mTOR-autophagy system. 査読 国際誌

    Daisuke Yamada, Kenji Kawabe, Ikue Tosa, Shunpei Tsukamoto, Ryota Nakazato, Miki Kou, Koichi Fujikawa, Saki Nakamura, Mitsuaki Ono, Toshitaka Oohashi, Mari Kaneko, Shioi Go, Eiichi Hinoi, Yukio Yoneda, Takeshi Takarada

    Communications biology2   346 - 346   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The pathophysiological role of mammalian target of rapamycin complex 1 (mTORC1) in neurodegenerative diseases is established, but possible therapeutic targets responsible for its activation in neurons must be explored. Here we identified solute carrier family 38a member 1 (SNAT1, Slc38a1) as a positive regulator of mTORC1 in neurons. Slc38a1
    flox/flox
    and Synapsin I-Cre mice were crossed to generate mutant mice in which Slc38a1 was selectively deleted in neurons. Measurement of 2,3,5-triphenyltetrazolium chloride (TTC) or the MAP2-negative area in a mouse model of middle cerebral artery occlusion (MCAO) revealed that Slc38a1 deficiency decreased infarct size. We found a transient increase in the phosphorylation of p70S6k1 (pp70S6k1) and a suppressive effect of rapamycin on infarct size in MCAO mice. Autophagy inhibitors completely mitigated the suppressive effect of SNAT1 deficiency on neuronal cell death under in vitro stroke culture conditions. These results demonstrate that SNAT1 promoted ischemic brain damage via mTOR-autophagy system.

    DOI: 10.1038/s42003-019-0582-4

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  • Commensal Microbiota Enhance Both Osteoclast and Osteoblast Activities. 査読

    Uchida Y, Irie K, Fukuhara D, Kataoka K, Hattori T, Ono M, Ekuni D, Kubota S, Morita M

    Molecules (Basel, Switzerland)23 ( 7 )   2018年6月

  • Physiological role of urothelial cancer-associated one long noncoding RNA in human skeletogenic cell differentiation. 査読 国際誌

    Takanori Ishikawa, Takashi Nishida, Mitsuaki Ono, Takeshi Takarada, Ha Thi Nguyen, Shinnosuke Kurihara, Takayuki Furumatsu, Yurika Murase, Masaharu Takigawa, Toshitaka Oohashi, Hiroshi Kamioka, Satoshi Kubota

    Journal of cellular physiology233 ( 6 ) 4825 - 4840   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A vast number of long-noncoding RNAs (lncRNA) are found expressed in human cells, which RNAs have been developed along with human evolution. However, the physiological functions of these lncRNAs remain mostly unknown. In the present study, we for the first time uncovered the fact that one of such lncRNAs plays a significant role in the differentiation of chondrocytes and, possibly, of osteoblasts differentiated from mesenchymal stem cells, which cells eventually construct the human skeleton. The urothelial cancer-associated 1 (UCA1) lncRNA is known to be associated with several human malignancies. Firstly, we confirmed that UCA1 was expressed in normal human chondrocytes, as well as in a human chondrocytic cell line; whereas it was not detected in human bone marrow mesenchymal stem cells (hBMSCs). Of note, although UCA1 expression was undetectable in hBMSCs, it was markedly induced along with the differentiation toward chondrocytes, suggesting its critical role in chondrogenesis. Consistent with this finding, silencing of the UCA1 gene significantly repressed the expression of chondrogenic genes in human chondrocytic cells. UCA1 gene silencing and hyper-expression also had a significant impact on the osteoblastic phenotype in a human cell line. Finally, forced expression of UCA1 in a murine chondrocyte precursor, which did not possess a UCA1 gene, overdrove its differentiation into chondrocytes. These results indicate a physiological and important role of this lncRNA in the skeletal development of humans, who require more sustained endochondral ossification and osteogenesis than do smaller vertebrates.

    DOI: 10.1002/jcp.26285

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  • Host-produced ADAMTS4 Inhibits Early-Stage Tumor Growth. 査読

    Keiichi Asano, Midori Edamatsu, Omer F Hatipoglu, Junko Inagaki, Mitsuaki Ono, Takashi Ohtsuki, Toshitaka Oohashi, Satoshi Hirohata

    Acta medica Okayama72 ( 3 ) 257 - 266   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Several research groups demonstrated that 'a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS)'-family proteases play roles in cancer progression. However, the origins and contributions of these proteases are not known. Here, we demonstrate an association between host-produced ADAMTS4 and early-stage tumor growth. Murine Lewis lung carcinoma (LLC) tumors showed marked expressions of Adamts4 and Adamts5. We examined the contributions and distributions of host-derived Adamts4 and Adamts5 on tumor growth, using Adamts4LacZ/LacZ and Adamts5LacZ/LacZ knockout mice. Interestingly, the Adamts4LacZ/LacZ mice showed enhanced tumor growth compared to wild-type mice at 5-, 10- and 12-days post-inoculation, whereas the Adamts5LacZ/LacZ mice did not show significant differences in tumor growth. We next examined LacZ distribution in LLC tumor-bearing Adamts4LacZ/LacZ mice by β-galactosidase (β-gal) staining. We found that the β-gal-positive signals were strictly localized at the interior areas of the tumor at 10 days post-inoculation. Multiple staining demonstrated that most of the β-gal-positive cells were localized at the tumor vasculature in Adamts4LacZ/LacZ mice. Interestingly, β-gal-positive signals were not co-localized with biglycan after 10 days post-inoculation, excluding the biglycan cleavage by host-derived ADAMTS4. Taken together, these findings illustrate that host-derived ADAMTS4 was expressed at the tumor vessels and was associated with early-stage tumor growth.

    DOI: 10.18926/AMO/56071

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  • Anti-HMGB1 neutralizing antibody attenuates periodontal inflammation and bone resorption in a murine periodontitis model 査読

    Chiaki Yoshihara-Hirata, Keisuke Yamashiro, Tadashi Yamamoto, Hiroaki Aoyagi, Hidetaka Ideguchi, Mari Kawamura, Risa Suzuki, Mitsuaki Ono, Hidenori Wake, Masahiro Nishibori, Shogo Takashiba

    Infection and Immunity86 ( 5 )   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Society for Microbiology  

    High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein that is secreted into the extracellular milieu in response to inflammatory stimuli. The secreted HMGB1 mediates various inflammatory diseases, including periodontitis
    however, the underlying mechanisms of HMGB1-induced periodontal inflammation are not completely understood. Here, we examined whether anti-HMGB1 neutralizing antibody inhibits periodontal progression and investigated the molecular pathology of HMGB1 in vitro and in vivo. In vitro analysis indicated that HMGB1, granulocytemacrophage colony-stimulating factor (GM-CSF), and interleukin-1β (IL-1β) were secreted in response to tumor necrosis factor-α (TNF-α) stimuli in human gingival epithelial cells (HGECs) and human monocytic leukemia cells (THP-1) treated with phorbol myristate acetate. Increased levels of GM-CSF and IL-1β were observed in the conditioned media from TNF-α-stimulated HGECs and THP-1 in vitro. Simultaneous stimulation with TNF-α and anti-HMGB1 antibody significantly decreased TNF-α- induced inflammatory cytokine secretion. Experimental periodontitis was induced in mice using Porphyromonas gingivalis-soaked ligatures. The extracellular translocation was confirmed in gingival epithelia in the periodontitis model mice by immunofluorescence analysis. Systemic administration of anti-HMGB1 neutralizing antibody significantly inhibited translocation of HMGB1. The anti-HMGB1 antibody inhibited periodontal inflammation, expression of IL-1β and C-X-C motif chemokine ligand 1 (CXCL1), migration of neutrophils, and bone resorption, shown by bioluminescence imaging of myeloperoxidase activity, quantitative reverse transcription-PCR (RT-PCR), and micro-computed tomography analysis. These findings indicate that HMGB1 is secreted in response to inflammatory stimuli caused by periodontal infection, which is crucial for the initiation of periodontitis, and the anti-HMGB1 antibody attenuates the secretion of a series of inflammatory cytokines, consequently suppressing the progression of periodontitis.

    DOI: 10.1128/IAI.00111-18

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  • Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma. 査読 国際誌

    Ayaka Morisawa, Tatsuo Okui, Tsuyoshi Shimo, Soichiro Ibaragi, Yuka Okusha, Mitsuaki Ono, Thi Thu Ha Nguyen, Nur Mohammad Monsur Hassan, Akira Sasaki

    International journal of oncology52 ( 3 ) 989 - 999   2018年3月

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    記述言語:英語  

    Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge clinically where one of the mechanisms responsible for the invasion into facial bones occurs via the activation of osteoclasts. Copper has been demonstrated to play a key role in skeletal remodeling. However, the role of copper in cancer-associated bone destruction is thus far unknown. Lysyl oxidase (LOX) is a copper-dependent enzyme that promotes osteoclastogenesis. In the present study, we investigated the effects of copper on HNSCC with bone invasion by the copper chelator, ammonium tetrathiomolybdate (TM) in vitro and in vivo. We demonstrate that TM blocks the proliferation of HNSCC cells, inhibits LOX activation and decreases the expression of the receptor activator of nuclear factor-κB ligand (RANKL) in osteoblasts and osteocytes, subsequently suppressing bone destruction. These findings suggest that copper is a potential target for the treatment of HNSCCs associated with bone destruction.

    DOI: 10.3892/ijo.2018.4242

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

    Ono M, Masaki A, Maeda A, Kilts TM, Hara ES, Komori T, Pham H, Kuboki T, Young MF

    Matrix biology : journal of the International Society for Matrix Biology68-69   533 - 546   2018年

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    掲載種別:研究論文(学術雑誌)  

    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. 査読

    Komori T, Ono M, Hara ES, Ueda J, Nguyen HTT, Nguyen HT, Yonezawa T, Maeba T, Kimura-Ono A, Takarada T, Momota R, Maekawa K, Kuboki T, Oohashi T

    Scientific reports8 ( 1 ) 2612   2018年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-018-21000-0

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

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

    Journal of Bone and Mineral Research34 ( 2 ) 327 - 332   2018年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/jbmr.3598

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

    Mitsuaki Ono, Masamitsu Oshima, Miho Ogawa, Wataru Sonoyama, Emilio Satoshi Hara, Yasutaka Oida, Shigehiko Shinkawa, Ryu Nakajima, Atsushi Mine, Satoru Hayano, Satoshi Fukumoto, Shohei Kasugai, Akira Yamaguchi, Takashi Tsuji, Takuo Kuboki

    Scientific Reports7   44522 - 44522   2017年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Nature  

    DOI: 10.1038/srep44522

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  • Analysis of CCN4 function in osteogenic and osteoclastic cells using gain and loss of function approaches 査読

    Azusa Maeda, Marian Young, Mitsuaki Ono

    Methods in Molecular Biology1489   347 - 359   2017年

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:Humana Press Inc.  

    Analysis of CCN4 function in bone was assessed using both gain and loss of function approaches. In mice this was done by genetic engineering and homologous recombination to create mice with complete ablation of the protein. For human skeletal cells adenoviral gene transfer and shRNA were used for gain and loss of function respectively. Here we describe procedures used to make and then analyze osteogenic and osteoclastic cells with or without CCN4 to determine its role in osteogenic differentiation.

    DOI: 10.1007/978-1-4939-6430-7_29

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

    Yoshioka Y, Ono M, Maeda A, Kilts TM, Hara ES, Khattab H, Ueda J, Aoyama E, Oohashi T, Takigawa M, Young MF, Kuboki T

    Bone83   162 - 170   2016年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bone.2015.11.007

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  • WNT1-induced Secreted Protein-1 (WISP1), a Novel Regulator of Bone Turnover and Wnt Signaling 査読

    Azusa Maeda, Mitsuaki Ono, Kenn Holmbeck, Li Li, Tina M. Kilts, Vardit Kram, Megan L. Noonan, Yuya Yoshioka, Erin M. B. McNerny, Margaret A. Tantillo, David H. Kohn, Karen M. Lyons, Pamela G. Robey, Marian F. Young

    JOURNAL OF BIOLOGICAL CHEMISTRY290 ( 22 ) 14004 - 14018   2015年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

    WISP1/CCN4 (hereafter referred to as WISP1), a member of the CCN family, is found in mineralized tissues and is produced by osteoblasts and their precursors. In this study, Wisp1-deficient (Wisp1(-/-)) mice were generated. Using dual-energy x-ray absorptiometry, we showed that by 3 months, the total bone mineral density of Wisp1(-/-) mice was significantly lower than that of WT mice. Further investigation by micro-computed tomography showed that female Wisp1(-/-) mice had decreased trabecular bone volume/total volume and that both male and female Wisp1(-/-) mice had decreased cortical bone thickness accompanied by diminished biomechanical strength. The molecular basis for decreased bone mass in Wisp1(-/-) mice arises from reduced bone formation likely caused by osteogenic progenitors that differentiate poorly compared with WT cells. Osteoclast precursors from Wisp1(-/-) mice developed more tartrate-resistant acid phosphatase-positive cells in vitro and in transplants, suggesting that WISP1 is also a negative regulator of osteoclast differentiation. When bone turnover (formation and resorption) was induced by ovariectomy, Wisp1(-/-) mice had lower bone mineral density compared WT mice, confirming the potential for multiple roles for WISP1 in controlling bone homeostasis. Wisp1(-/-) bone marrow stromal cells had reduced expression of beta-catenin and its target genes, potentially caused by WISP1 inhibition of SOST binding to LRP6. Taken together, our data suggest that the decreased bone mass found in Wisp1(-/-) mice could potentially be caused by an insufficiency in the osteodifferentiation capacity of bone marrow stromal cells arising from diminished Wnt signaling, ultimately leading to altered bone turnover and weaker biomechanically compromised bones.

    DOI: 10.1074/jbc.M114.628818

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  • Topical Application of Lithium Chloride on the Pulp Induces Dentin Regeneration 査読

    Kazuya Ishimoto, Satoru Hayano, Takeshi Yanagita, Hiroshi Kurosaka, Noriaki Kawanabe, Shinsuke Itoh, Mitsuaki Ono, Takuo Kuboki, Hiroshi Kamioka, Takashi Yamashiro

    PLOS ONE10 ( 3 ) e0121938   2015年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    We herein describe a novel procedure for dentin regeneration that mimics the biological processes of tooth development in nature. The canonical Wnt signaling pathway is an important regulator of the Dentin sialophosphoprotein (Dspp) expression. Our approach mimics the biological processes underlying tooth development in nature and focuses on the activation of canonical Wnt signaling to trigger the natural process of dentinogenesis. The coronal portion of the dentin and the underlying pulp was removed from the first molars. We applied lithium chloride (LiCl), an activator of canonical Wnt signaling, on the amputated pulp surface to achieve transdifferentiation toward odontoblasts from the surrounding pulpal cells. MicroCT and microscopic analyses demonstrated that the topical application of LiCl induced dentin repair, including the formation of a complete dentin bridge. LiCl-induced dentin is a tubular dentin in which the pulp cells are not embedded within the matrix, as in primary dentin. In contrast, a dentin bridge was not induced in the control group treated with pulp capping with material carriers alone, although osteodentin without tubular formation was induced at a comparatively deeper position from the pulp exposure site. We also evaluated the influence of LiCl on differentiation toward odontoblasts in vitro. In the mDP odontoblast cell line, LiCl activated the mRNA expression of Dspp, Axin2 and Kallikrein 4 (Klk4) and downregulated the Osteopontin (Osp) expression. These results provide a scientific basis for the biomimetic regeneration of dentin using LiCl as a new capping material to activate dentine regeneration.

    DOI: 10.1371/journal.pone.0121938

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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. 査読

    Hara ES, Ono M, Pham HT, Sonoyama W, Kubota S, Takigawa M, Matsumoto T, Young MF, Olsen BR, Kuboki T

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research30 ( 9 ) 1585 - 1596   2015年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/jbmr.2502

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

    Hara ES, Ono M, Yoshioka Y, Ueda J, Hazehara Y, Pham HT, Matsumoto T, Kuboki T

    Cells, tissues, organs201 ( 2 ) 88 - 96   2015年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000442411

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  • The BMP2 antagonist inhibitor L51P enhances the osteogenic potential of BMP2 by simultaneous and delayed synergism 査読

    Hany Mohamed Khattab, Mitsuaki Ono, Wataru Sonoyama, Yasutaka Oida, Shigehiko Shinkawa, Yuya Yoshioka, Kenji Maekawa, Yasuhiko Tabata, Kazushige Sugama, Walter Sebald, Talmo Kuboki

    BONE69   165 - 173   2014年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Bone morphogenetic protein 2 (BMP2) is a potent osteoinductive cytokine that plays crucial roles in bone repair. However, large amounts of BMP2 are required to induce sufficient bone formation in humans possibly due to a feedback response of BMP antagonists. The engineered BMP2 variant L51P is deficient in BMP receptor type I activation but maintains affinity for BMP antagonists and can allow for the inactivation of BMP antagonists, and eventually enhance BMP2 action. As hypothesized, simultaneous addition of L51P enhanced the BMP2-induced osteogenesis. To test the ability of L51P to competitively inactivate BMP antagonists, cell binding affinity of BMP2 ligands was investigated in the presence or absence of L51P. Because the BMP antagonists were highly expressed 3 days after exogenous BMP2 stimulation, we collected supernatants from 3-day stimulated cell cultures and used as condition culture media (CM). The results showed a significant decrease in the cell binding of BMP2 ligands when cells were incubated with exogenous BMP2 and CM, whereas L51P addition competitively rescued the suppression of BMP2-to-cell binding induced by CM incubation. In a delayed experimental model, L51P was applied 3 days after exogenous BMP2 stimulation and we could observe a striking enhancement of the BMP2-induced SMAD-1/5/8 phosphorylation and luciferase activity of the Id1 promoter compared to the simultaneous addition of the two factors. These findings provide a deeper insight into the cellular and molecular mechanisms involved in the effect of L51P in suppressing the BMP antagonists and enhancing BMP activity. Additionally, these results demonstrate that L51P is a promising down regulator of BMP-induced negative feedback, which could have a significant impact in future applications of BMP2 in research and clinical settings. (C) 2014 Elsevier Inc. All rights reserved.

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

    Abd El Kader, T., Kubota, S., Nishida, T., Hattori, T., Aoyama, E., Janune, D., Hara, E.S., Ono, M., Tabata, Y., Kuboki, T., Takigawa, M.

    Bone59   180 - 188   2014年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bone.2013.11.010

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

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

    Stem Cell Research & Therapy5 ( 1 ) 31   2014年

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    掲載種別:研究論文(学術雑誌)  

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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. 査読

    Ono M, Sonoyama W, Yamamoto K, Oida Y, Akiyama K, Shinkawa S, Nakajima R, Pham HT, Hara ES, Kuboki T

    Cells, tissues, organs199 ( 4 ) 249 - 255   2014年

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    掲載種別:研究論文(学術雑誌)  

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  • WISP1/CCN4: A Potential Target for Inhibiting Prostate Cancer Growth and Spread to Bone 査読

    Mitsuaki Ono, Colette A. Inkson, Robert Sonn, Tina M. Kilts, Luis F. de Castro, Azusa Maeda, Larry W. Fisher, Pamela G. Robey, Agnes D. Berendsen, Li Li, Nancy McCartney-Francis, Aaron C. Brown, Nigel P. S. Crawford, Alfredo Molinolo, Alka Jain, Neal S. Fedarko, Marian F. Young

    PLoS ONE8 ( 8 ) e71709   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Prostate cancer (PC) is a leading cause of death in men however the factors that regulate its progression and eventual metastasis to bone remain unclear. Here we show that WISP1/CCN4 expression in prostate cancer tissues was up-regulated in early stages of the disease and, further, that it correlated with increased circulating levels of WISP1 in the sera of patients at early stages of the disease. WISP1 was also elevated in the mouse prostate cancer model TRAMP in the hypoplastic diseased tissue that develops prior to advanced carcinoma formation. When the ability of anti-WISP1 antibodies to reduce the spread of PC3-Luc cells to distant sites was tested it showed that twice weekly injections of anti-WISP1 antibodies reduced the number and overall size of distant tumors developed after intracardiac (IC) injection of PC3-Luc cells in mice. The ability of antibodies against WISP1 to inhibit growth of PC3-Luc cancer cells in mice was also evaluated and showed that twice weekly injections of anti-WISP1 antibodies reduced local tumor growth when examined in xenografts. To better understand the mechanism of action, the migration of PC3-Luc cells through membranes with or without a Matrigel™ barrier showed the cells were attracted to WISP1, and that this attraction was inhibited by treatment with anti-WISP1 antibodies. We also show the expression of WISP1 at the bone-tumor interface and in the stroma of early grade cancers suggested WISP1 expression is well placed to play roles in both fostering growth of the cancer and its spread to bone. In summary, the up-regulation of WISP1 in the early stages of cancer development coupled with its ability to inhibit spread and growth of prostate cancer cells makes it both a potential target and an accessible diagnostic marker for prostate cancer.

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  • Regeneration of Calvarial Defects with Escherichia coli-Derived rhBMP-2 Adsorbed in PLGA Membrane 査読

    Ono, Mitsuaki, Sonoyama, Wataru, Nema, Kazuki, Hara, Emilio Satoshi, Oida, Yasutaka, Hai Thanh Pham, Yamamoto, Katushi, Hirota, Kazuo, Sugama, Kazushige, Sebald, Walter, Kuboki, Takuo

    Cells Tissues Organs198 ( 5 ) 367 - 376   2013年

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    掲載種別:研究論文(学術雑誌)  

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

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

    Biochimie95 ( 2 ) 374 - 381   2013年

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    掲載種別:研究論文(学術雑誌)  

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  • OstemiR: a novel panel of microRNA biomarkers in osteoblastic and osteocytic differentiation from mesencymal stem cells. 査読

    Eguchi T, Watanabe K, Hara ES, Ono M, Kuboki T, Calderwood SK

    PloS one8 ( 3 ) e58796   2013年

  • miRNA-720 Controls Stem Cell Phenotype, Proliferation and Differentiation of Human Dental Pulp Cells 査読

    Hara, Emilio Satoshi, Ono, Mitsuaki, Eguchi, Takanori, Kubota, Satoshi, Hai Thanh Pham, Sonoyama, Wataru, Tajima, Shoji, Takigawa, Masaharu, Calderwood, Stuart K., Kuboki, Takuo

    Plos One8 ( 12 ) e83545   2013年

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    掲載種別:研究論文(学術雑誌)  

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  • Stage-specific embryonic antigen-4 identifies human dental pulp stem cells 査読

    Noriaki Kawanabe, Satoko Murata, Hiroaki Fukushima, Yoshihito Ishihara, Takeshi Yanagita, Emmy Yanagita, Mitsuaki Ono, Hiroshi Kurosaka, Hiroshi Kamioka, Tomoo Itoh, Takuo Kuboki, Takashi Yamashiro

    EXPERIMENTAL CELL RESEARCH318 ( 5 ) 453 - 463   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER INC  

    Embryonic stem cell-associated antigens are expressed in a variety of adult stem cells as well as embryonic stem cells. In the present study, we investigated whether stage-specific embryonic antigen (SSEA)-4 can be used to isolate dental pulp (DP) stem cells. DP cells showed plastic adherence, specific surface antigen expression, and multipotent differentiation potential, similar to mesenchymal stem cells (MSC). SSEA-4+ cells were found in cultured DP cells in vitro as well as in DP tissue in vivo. Flow cytometric analysis demonstrated that 45.5% of the DP cells were SSEA-4+. When the DP cells were cultured in the presence of all-trans-retinoic acid, marked downregulation of SSEA-3 and SSEA-4 and the upregulation of SSEA-1 were observed. SSEA-4+ DP cells showed a greater telomere length and a higher growth rate compared to ungated and SSEA-4 - cells. A clonal assay demonstrated that 65.5% of the SSEA-4+ DP cells had osteogenic potential, and the SSEA-4+ clonal DP cells showed multilineage differentiation potential toward osteoblasts, chondrocytes, and neurons in vitro. In addition, the SSEA-4+ DP cells had the capacity to form ectopic bone in vivo. Thus, our results suggest that SSEA-4 is a specific cell surface antigen that can be used to identify DP stem cells. (C) 2012 Elsevier Inc. All rights reserved.

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  • Infuence of resin coating materials on porphyromonas gingivalis attachment 査読

    Ai Kumada, Yoshizo Matsuka, Atsushi Mine, Mitsuaki Ono, Junji Uehara, Norihiro Sonoi, Takashi Ito, Shogo Takashiba, Takuo Kuboki

    Dental Materials Journal31 ( 1 ) 86 - 91   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Resin coating materials have been used for composite resin or provisional restoration in order to prevent plaque accumulation on their surfaces. However, it is not clear whether the coating materials infuence attachment of periodontal bacteria. Therefore, we investigated the effect of resin coating materials on the attachment of Porphyromonas gingivalis (Pg). The polymerized auto cure resin plates were coated with two resin coating materials. To estimate the Pg attachment, each plate was immersed in brain heart infusion medium containing Pg. The quantity of bacteria attached on each plate was evaluated by crystal violet quantifcation. Morphological change of Pg was recorded using scanning electron microscopy. Both coating groups presented signifcantly lower Pg attachment compared to the control. The Pg shapes on the plates with resin coating materials were similar to the non-treated control plates. The resin coating materials clearly prevent Pg attachment on the polymerized auto cure resin plate.

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  • WISP-1/CCN4 Regulates Osteogenesis by Enhancing BMP-2 Activity 査読

    Mitsuaki Ono, Colette A. Inkson, Tina M. Kilts, Marian F. Young

    JOURNAL OF BONE AND MINERAL RESEARCH26 ( 1 ) 193 - 208   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Wnt-induced secreted protein 1 (WISP-1/CCN4) is a member of the CCN family that is highly expressed in skeletal tissue and in osteoprogenitor cells induced to differentiate in vitro. To determine the function of WISP-1 during osteogeneis, osteogenic bone marrow stromal cells (BMSCs) were transduced with WISP-1 adenovirus (ad WISP-1) in the presence or absence of bone morphogenetic protein 2 (BMP-2) adenovirus (adBMP-2). WISP-1 overexpression enhanced the ability of BMP-2 to direct BMSCs toward osteogenic differentiation and appeared to work by stimulating Smad-1/5/8 phosphorylation and activation. The ability of WISP-1 to enhance BMP-2 activity also was shown in vivo using an ectopic osteogenesis assay with BMSCs transduced with WISP-1, BMP-2, or both. When BMSCs were infected with lentivirus containing human WISP1 shRNA, they formed less bone in vivo and were less responsive to BMP-2, confirming that WISP-1 and BMP-2 have a functional interaction. Immunoprecipitation (IP) and Western blot analysis showed that WISP-1 bound directly to BMP-2 and showed that WISP-1 increased BMP-2 binding to hBMSCs in a dose-dependent fashion. To understand how WISP-1 enhanced BMP-2 signaling, the influence of WISP-1 on integrin expression was analyzed. WISP-1 induced the mRNA and protein levels of alpha(5)-integrin and, further, was found to bind to it. Antibody-blocking experiments showed that the BMP-2 binding to BMSCs that was enhanced by WISP-1 was completely neutralized by treatment with anti-integrin alpha(5)beta(1) antibody. Pilot studies and the use of transgenic mice that overexpressed human WISP-1 in preosteoblasts had increased bone mineral density (BMD), trabecular thickness, and bone volume (BV/TV) over wild-type controls, supporting observations using human osteoprogenitors that WISP-1 has a positive influence on osteogenesis in vivo. In conclusion, these studies show, for the first time, that WISP-1 has a. positive influence on bone cell differentiation and function and may work by enhancing the effects of BMP-2 to increase osteogenesis through a mechanism potentially involving binding to integrin alpha(5)beta(1). (C) 2011 American Society for Bone and Mineral Research.

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  • Biglycan and Fibromodulin Have Essential Roles in Regulating Chondrogenesis and Extracellular Matrix Turnover in Temporomandibular Joint Osteoarthritis 査読

    Mildred C. Embree, Tina M. Kilts, Mitsuaki Ono, Colette A. Inkson, Fatima Syed-Picard, Morten A. Karsdal, Ake Oldberg, Yanming Bi, Marian F. Young

    AMERICAN JOURNAL OF PATHOLOGY176 ( 2 ) 812 - 826   2010年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC INVESTIGATIVE PATHOLOGY, INC  

    The temporomandibular joint is critical for jaw movements and allows for mastication, digestion of food, and speech. Temporomandibular joint osteoarthritis is a degenerative disease that is marked by permanent cartilage destruction and loss of extracellular matrix (ECM). To understand how the ECM regulates mandibular condylar chondrocyte (MCC) differentiation and function, we used a genetic mouse model of temporomandibular joint osteoarthritis that is deficient in two ECM proteins, biglycan and fibromodulin (Bgn(-/o) Fmod(-/-)). Given the unavailability of cell lines, we first isolated primary MCCs and found that they were phenotypically unique from hyaline articular chondrocytes isolated from the knee joint. Using Bgn(-/o) Fmod(-/-) MCCs, we discovered the early basis for temporomandibular joint osteoarthritis arises from abnormal and accelerated chondrogenesis. Transforming growth factor (TGF)-beta 1 is a growth factor that is critical for chondrogenesis and binds to both biglycan and fibromodulin. Our studies revealed the sequestration of TGF-beta 1 was decreased within the ECM of Bgn(-/o)Fmod(-/-) MCCs, leading to overactive TGF-beta 1 signal transduction. Using an explant culture system, we found that overactive TGF-beta 1 signals induced chondrogenesis and ECM turnover in this model. We demonstrated for the first time a comprehensive study revealing the importance of the ECM in maintaining the mandibular condylar cartilage integrity and identified biglycan and fibromodulin as novel key players in regulating chondrogenesis and ECM turnover during temoporomandibular joint osteoarthritis pathology. (Am J Pathol 2010, 176:812-826; DO: 10.2353/ajpath.2010.090450)

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  • Simvastatin Induces the Odontogenic Differentiation of Human Dental Pulp Stem Cells In Vitro and In Vivo 査読

    Yosuke Okamoto, Wataru Sonoyama, Mitsuaki Ono, Kentaro Akiyama, Takuo Fujisawa, Masamitstu Oshima, Yohei Tsuchimoto, Yoshizo Matsuka, Tatsuji Yasuda, Songtao Shi, Takuo Kuboki

    JOURNAL OF ENDODONTICS35 ( 3 ) 367 - 372   2009年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Statin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is known to promote bone formation. However, it is not clear whether statin affects the differentiation of pulp cells. This study used a cell proliferation assay, cell cycle analysis, quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and in vivo transplantation to examine the effects of simvastatin on human dental pulp stem cells (DPSCs) in vitro and in vivo. Simvastatin at 1 mu mol/L was able to significantly suppress the proliferation of DPSCs without inducing apoptosis. Quantitative RT-PCR revealed both osteocalcin and dentin sialophosphoprotein to be significantly up-regulated when DPSCs were cultured with simvastatin in comparison to bone morphogenetic protein-2 treatment. The in vivo transplantation data showed that simvastatin treatment promoted mineralized tissue formation. Taken together, these results suggest that statin might be an ideal active ingredient to accelerate the differentiation of DPSCs. (J Endod 2009;35:367-372)

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  • The Potential Functional Interaction of Biglycan and WISP-1 in Controlling Differentiation and Proliferation of Osteogenic Cells 査読

    Colette A. Inkson, Mitsuaki Ono, Yanming Bi, Sergei A. Kuznetsov, Larry W. Fisher, Marian F. Young

    CELLS TISSUES ORGANS189 ( 1-4 ) 153 - 157   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Biglycan ( BGN) and WISP-1 are 2 extracellular matrix proteins that bind to each other and colocalize in mineralizing tissue. Here we show that WISP-1 abrogates the repression of proliferation in bone marrow stromal cells induced by BGN. We also demonstrate that WISP-1 and its variant WISP-1va can alleviate the repressed osteogenic differentiation caused by the absence of BGN. These preliminary data suggest that WISP-1 and BGN may functionally interact and control each other's activity, thus regulating the differentiation and proliferation of osteogenic cells. Copyright (C) 2008 S. Karger AG, Basel

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  • Fibromodulin-Deficient Mice Reveal Dual Functions for Fibromodulin in Regulating Dental Tissue and Alveolar Bone Formation 査読

    Michel Goldberg, Mitsuaki Ono, Dominique Septier, Mireille Bonnefoix, Tina M. Kilts, Yanming Bi, Mildred Embree, Laurent Ameye, Marian F. Young

    CELLS TISSUES ORGANS189 ( 1-4 ) 198 - 202   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    The extracellular matrix of newborn, 7- and 21-day-old fibromodulin-deficient (Fmod KO) mice was compared with age-matched wild-type (WT) mice. Western blotting of proteins from 21-day-old WT mice revealed that the molecular weight of Fmod is smaller in dental tissues (approx. 40 kDa) compared to alveolar bone extracts (approx. 52 kDa). Dentin matrix protein1 (DMP1) was slightly increased in Fmod KO versus WT tooth extracts. After chondroitinase ABC digestion, dentin sialophosphoprotein (DSPP) appeared as 2 strong bands (approx. 150 and 70 kDa) in incisors from 21-day-old Fmod KO mice, whereas the smaller-sized species of DSPP was nearly absent in WT molars and no difference was detected between WT and KO mice in molars. Dentin mineralization was altered in newborn and 7-day-old KO mice, but seemed normal in 21-day-old KO mice. DMP1 and DSPP may be involved in compensatory mechanisms. The enamel had a twisted appearance and looked porous at day 21 in KO incisor, and the outer aprismatic layer was missing in the molar. Alveolar bone formation was enhanced in Fmod KO mice at days 0 and 7, whereas no difference was detected at day 21. We conclude that Fmod may control dental tissue formation and early maturation, where it acts mostly as an inhibitor in alveolar bone accumulation, excerpting its effects only at early developing stages. These dual functions may be related to the different forms of Fmod found in bone versus teeth. Copyright (C) 2008 S. Karger AG, Basel

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  • TGF-beta 1 and WISP-1/CCN-4 can regulate each other's activity to cooperatively control osteoblast function 査読

    Colette A. Inkson, Mitsuaki Ono, Sergei A. Kuznetsov, Larry W. Fisher, Pamela Gehron Robey, Marian F. Young

    JOURNAL OF CELLULAR BIOCHEMISTRY104 ( 5 ) 1865 - 1878   2008年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    Wnt-induced secreted protein-1 (WISP-1), likeother members of the CCN family, is expressed in skeletal tissues. Its mechanism of action remains unknown. Expression of WISP-1 was analyzed in human bone marrow stroma cells (hBMSC) by RT-PCR. We identified two major transcripts corresponding to those Of full-length WISP-1, and of the splice variant WISP-1va which lacks a putative BMP/TGF-beta binding site. To investigate the function Of WISP-1 in bone, hBMSC cultures were treated with recombinant human (rh)WISP-1 and analyzed for proliferation and osteogenic differentiation. WISP-1 treatment increased both BrdU incorporation and alkaline phosphatase (AP) activity. Considering the known functional synergy found between the TGF-beta super-family and members of the CCN family, we next tested the effect of WISP-1 on TGF-beta 1 activity. We found that rhWISP-1 could reduce rhTGF-beta 1 induced BrdU incorporation. Similarly, rhTGF-beta 1 inhibited rhWISP-1 induction of AP activity. To explore functional differences between the WISP-1 variants, WISP-1 or WISP-1va were transfected into hBMSC. Both variants could strongly induce BrdU incorporation. However, there were no effects of either variant on AP activity without an additional osteogenic Stimulus Such as TGF-beta 1. Taken together Our results suggest a functional relationship between WISP-1 and TGF-beta 1. To further define this relationship we analyzed the effect of WISP-1 on TGF-beta signaling. rhWISP-1 significantly reduced TGF-beta 1 induced phosphorylation of Smad-2. Our data indicates that full-length WISP-1 and its variant WISP-1va are modulators of proliferation and osteogenic differentiation, and may be novel regulators of TGF-beta 1 signaling in osteoblast-like cells.

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  • Promotion of hydroxyapatite-associated, stem cell-based bone regeneration by CCN2 査読

    Mitsuaki Ono, Satoshi Kubota, Takuo Fujisawa, Wataru Sonoyama, Harumi Kawakij, Kentaro Akiyama, Kengo Shimono, Masarnitsu Oshima, Takashi Nishida, Yasuhiro Yoshida, Kazuomi Suzuki, Masaharu Takigawa, Takuo Kuboki

    CELL TRANSPLANTATION17 ( 1-2 ) 231 - 240   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:COGNIZANT COMMUNICATION CORP  

    Multiple roles have been already recognized for CCN2 in cartilage development and regeneration. However, the effects of CCN2 on bone regeneration remain to be elucidated. In this study, the utility of CCN2 on bone regeneration was examined in vitro and in vivo in combination with hydroxyapatite (HAp) as a scaffold. Human bone marrow stromal cells (hBMSCs) were isolated from human iliac bone marrow aspirates of healthy donors and expanded, and the effects of CCN2 on their proliferation and migration were examined in vitro. The proliferation of hBMSCs on a plastic or HAp plate was significantly enhanced by CCN2. Moreover, the migration of hBMSCs also dramatically increased by CCN2. Interestingly, a C-terminal signal modular fragment of CCN2 (CT-module) also enhanced the cell proliferation and migration as efficiently as the full-length CCN2. Next, in order to estimate the effect of CCN2 on the migration and survival of hBMSCs and bone formation inside the HAp scaffold in vivo, two experiments were performed. First, the porous HAp carrier was cultured with hBMSCs for a week, and the cell-scaffold hybrid was transplanted with or without CCN2 subcutaneously into immunocompromised mice. CCN2 accelerated the hBMSC-like cell migration and survival inside the porous HAp within 4 weeks after transplantation. Second, the porous HAp carrier with or without CCN2 was directly implanted into bone defects within a rabbit mandible, and bone regeneration inside was evaluated. As a result, CCN2 efficiently induced the cell invasion and bone formation inside the porous HAp scaffold. These findings suggest that CCN2 and its CT-module fragment could be useful for regeneration and reconstruction of large-scale bone defects.

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  • Promotion of attachment of human bone marrow stromal cells by CCN2 査読

    Mitsuaki Ono, Satoshi Kubota, Takuo Fujisawa, Wataru Sonoyama, Harumi Kawaki, Kentaro Akiyama, Masamitsu Oshima, Takashi Nishida, Yasuhlro Yoshida, Kazuomi Suzuki, Masaharu Takigawa, Takuo Kuboki

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS357 ( 1 ) 20 - 25   2007年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Cell attachment is a crucial step in tissue regeneration. In this study, human bone marrow stromal cells (hBMSCs) were isolated, and the effects of CCN2 on their attachment were examined. CCN2 significantly enhanced the hBMSC attachment, and this enhanced cell attachment was mainly regulated by the C-terminal module of CCN2. This enhancement was negated by the anti-integrin alpha(v)beta(3) antibody and p38 MAPK inhibitor, and phosphorylation of p38 MAPK was detected upon the enhanced cell attachment mediated by CCN2. We thus conclude that CCN2 enhances hBMSC attachment via integrin-p38 MAPK signal pathway. Enhanced hBMSC attachment on hydroxyapatite plates by CCN2 further indicated the utility of CCN2 in bone regeneration. (c) 2007 Elsevier Inc. All rights reserved.

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▼全件表示

産業財産権

  • 角化歯肉誘導剤

    窪木拓男, 大野充昭, 前川賢治, 植田淳二, 小盛大志

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    出願番号:特願2016-113309  出願日:2016年

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  • 骨形成促進剤

    窪木拓男, 大野充昭, ファン タン ハイ, エミリオ サトシ ハラ

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    出願番号:特願2015-69222  出願日:2015年

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  • 軟骨再生促進剤

    窪木拓男, エミリオ サトシ ハラ, 大野充昭, 園山 亘, 滝川正春

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    出願番号:特願2011-037932  出願日:2011年

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  • 人工骨膜

    窪木拓男, 園山 亘, 大野充昭, 笈田育尚, 山本克史

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    出願番号:特願2011-113498  出願日:2011年

    特許番号/登録番号:特許5924610  発行日:2016年

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受賞

  • 日本補綴歯科学会,Kavo Dental Award

    2018年  

    大野充昭

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  • 岡山歯学会 平成30年度 最優秀論文賞

    2018年  

    大野充昭

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  • 第47回日本口腔インプラント学会,優秀演題賞

    2017年  

    大野充昭

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  • 岡山大学若手トップリサーチャー研究奨励賞

    2016年  

    大野充昭

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  • 日本口腔インプラント学会,優秀演題賞

    2015年  

    大野充昭

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  • 日本補綴歯科学会学術大会,課題口演最優秀賞

    2014年  

    大野充昭

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  • JADR学術大会,JADR/ GC Young Investigator Award

    2013年  

    大野充昭

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  • 日本補綴歯科学会,Kavo Dental Award

    2013年  

    大野充昭

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  • 日本口腔インプラント学会,優秀演題賞

    2013年  

    大野充昭

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  • 日本骨代謝学会学術集会 優秀演題賞

    2010年  

    大野充昭

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  • アメリカ骨代謝学会 Young Invesitator Award受賞

    2009年  

    大野充昭

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  • JADR学術大会JADR/GC Young Investigator Award

    2006年  

    大野充昭

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共同研究・競争的資金等の研究

  • 生理的歯の再生に向けた象牙芽細胞マスター遺伝子の探索

    2017年04月 - 2018年03月

    公益財団法人岡山医学振興会第17回公募助成金 

    大野充昭

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    担当区分:研究代表者  資金種別:競争的資金

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  • BMP−2の環境選択的骨誘導/抑制メカニズムの解明・応用に基づく骨再生療法 の開発

    2016年04月 - 2019年03月

    基盤研究(B) 

    大野充昭

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    担当区分:研究代表者  資金種別:競争的資金

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  • iPS細胞樹立技術を応用した象牙芽細胞マスター遺伝子の探索

    2016年04月 - 2018年03月

    挑戦的萌芽研究 

    大野充昭

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    担当区分:研究代表者  資金種別:競争的資金

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  • 健全な歯周組織再生を目的とした角化歯肉誘導治療薬の開発

    2015年04月 - 2017年03月

    AMED  橋渡し研究加速ネットワークプログラム(シーズA) 

    大野充昭

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    担当区分:研究代表者  資金種別:競争的資金

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  • 間葉系幹細胞ニッチという観点から見た歯槽骨創傷治癒メカニズムの解明

    2013年04月 - 2016年03月

    若手研究B 

    大野充昭

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    担当区分:研究代表者  資金種別:競争的資金

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  • 変形性関節症ならびに軟骨分化におけるWISP-1遺伝子の機能解析

    2010年04月 - 2012年03月

    研究活動スタート支援 

    大野充昭

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    担当区分:研究代表者  資金種別:競争的資金

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担当授業科目

  • 分子医化学 (2020年度) 特別  - その他

  • 分子医化学I(演習・実習) (2020年度) 特別  - その他

  • 分子医化学I(講義・演習) (2020年度) 特別  - その他

  • 分子医化学II(演習・実習) (2020年度) 特別  - その他

  • 分子医化学II(講義・演習) (2020年度) 特別  - その他

  • 機能的咬合系の成り立ちと顎関節症 (2020年度) 第1学期  - 水4

  • 生化学 (2020年度) 集中  - その他

  • 生化学・分子医化学実習 (2020年度) 特別  - その他

▼全件表示