Nano Biomedicine
Online ISSN : 2185-4734
Print ISSN : 1883-5198
ISSN-L : 1883-5198
Current issue
Displaying 1-9 of 9 articles from this issue
MINI REVIEW
ORIGINAL ARTICLE
  • Ayumu MORISAKI, Hiroshi INOUE, Seiji GODA
    2023 Volume 15 Issue 2 Pages 44-50
    Published: 2023
    Released on J-STAGE: January 19, 2024
    JOURNAL OPEN ACCESS

    Matrix metalloproteinases degrade the extracellular matrix during remodeling, and their activity is regulated by tissue metalloproteinase inhibitors (TIMPs). Platelet-derived growth factor (PDGF) is produced in periodontal tissue and is an important regulator of wound healing and tissue repair. ERK1/2, members of the MAPK family, are intracellular signaling substance kinases involved in TIMP-1 production. To elucidate the mechanisms underlying connective tissue remodeling, the present study investigated the relationship between PDGF-bb-stimulated TIMP-1 production and ERK1/2 phosphorylation in human gingival fibroblasts (HGF). TIMP-1 production increased in a PDGF-bb concentration-dependent manner. PDGF-bb-induced increases in TIMP-1 were further enhanced by the p38α/β inhibitor SB239063 and p38α-siRNA. The PDGF-bb stimulation also induced the phosphorylation of ERK1/2. In contrast, the treatment with the p38-MAPK inhibitor SB203580 suppressed the phosphorylation of ERK1/2. These results suggest that PDGF-bb induced the production of TIMP-1 through the ERK1/2-activated signal transduction pathway in HGF. In addition, signaling cross-talk between p38α and ERK1/2 was involved in ERK1/2 activation, suggesting that ERK1/2 activation is coordinately regulated by p38α.

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  • Hitomi NAKAMA, Masataka YOSHIKAWA, Nozomi MATSUO, Hiroshi MAEDA
    2023 Volume 15 Issue 2 Pages 51-65
    Published: 2023
    Released on J-STAGE: January 19, 2024
    JOURNAL OPEN ACCESS

    The present study attempted to obtain factors that induce the calcified nodule formation in a mesenchymal stem cell (MSC) culture through the aggregation of micro- or nanoparticles, such as calcium carbonate. There are few suitable cell sources in the oral cavity other than dental pulp tissue, from which only a small number of MSCs may be obtained. However, a large number of MSCs are needed for tooth regeneration. Therefore, factors that promote MSC proliferation and differentiation are required. Vitamin B1 (VB1), vitamin B3 (VB3) and vitamin B5 (VB5), which are present in physiologically active substances, were selected and investigated their effects to bone formation in vitro. VB1 and VB3 significantly increased the ability of dexamethasone (Dex) to form calcified nodule aggregates in vitro, whereas VB5 exerted the opposite effects. Therefore, it was confirmed from the results of this in vitro study that VB1 and VB3 may affect to Dex to promote MSCs in rat bone marrow cells for proliferation and differentiation into hard tissue-forming cells and the formation of calcified nodule aggregates.

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  • Akito FUKAWA, Hiroshi INOUE, Aki NISHIURA, Seiji GODA, Naoyuki MATSUMO ...
    2023 Volume 15 Issue 2 Pages 66-74
    Published: 2023
    Released on J-STAGE: January 19, 2024
    JOURNAL OPEN ACCESS

    In orthodontic treatment, tooth movement occurs based on bone remodeling in response to orthodontic forces. Interleukin-17A (IL-17) is a proinflammatory cytokine that is primarily secreted by Th 17 cells. In the present study, we investigated the mechanisms by which transforming growth factor β-activated kinase 1 (TAK1) inhibits osteoclast differentiation and the role of IL-17 in the intracellular signaling pathways IκB kinase α (IKKα) and nuclear factor-κB (NF-κB) p65, which are downstream of mitogen-activated protein kinases (MAPKs) (p38 and c-Jun N-terminal kinases (JNK)). We confirmed that IL-17 dose-dependently suppressed tartrate-resistant acid phosphatase (TRAP) activity in RAW264.7 cells in the presence of receptor for activation of NF-κB ligand (RANKL). We also found that a treatment with takinib, a potent and selective TAK1 inhibitor, significantly inhibited RANKL-stimulated TRAP activity in RAW264.7 cells. Furthermore, we demonstrated that IL-17 reduced the phosphorylation of TAK1, IKKα, and NF-κB p65. Collectively, these results suggest that IL-17 suppressed RANKL-induced osteoclast differentiation by inhibiting the canonical NF-κB pathway via TAK1. Therefore, IL-17 may be one of the factors suppressing RANKL-induced osteoclast differentiation. In the future, we would like to contribute to the development of reagents that locally control osteoclast differentiation by combining with nanocapsules that selectively deliver IL-17 to osteoclast progenitor cells.

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  • Miaki UZU, Toshiaki TAKEZAWA
    2023 Volume 15 Issue 2 Pages 75-87
    Published: 2023
    Released on J-STAGE: January 19, 2024
    JOURNAL OPEN ACCESS

    It is necessary to develop an evaluating system for the biliary excretion of compounds for predicting drug-induced liver injury that is a major adverse event leading to drug halt and drug withdrawals. The sandwich-cultured hepatocytes do not reflect hepatic events in vivo due to using Ca2+-free buffer although they were used to estimate the biliary excretion of compounds. Here, we aimed to develop a novel culture technology that can extrapolate the excretion of drug metabolites in the liver into the bile duct using the crosstalk between HepG2-NIAS cells (a human hepatocellular carcinoma cell line) forming bile canaliculus-like structures (BCLSs) in a collagen vitrigel membrane chamber and monolayered TFK-1 cells (a human bile duct carcinoma cell line) in a plate-well. In the co-culture system of HepG2-NIAS cells and TFK-1 cells, the total excretion amount of fluorescein accumulated in BCLSs and its excretion rate towards the plate-well represented a time-dependent increase after HepG2-NIAS cells were exposed to fluorescein diacetate. In contrast, the co-culture system of HepG2-NIAS cells and monolayered cells of HUVECs (human umbilical vein endothelial cells) or HDFs (human dermal fibroblasts) did not increase the excretion rate of fluorescein towards the plate-well. The selective excretion of fluorescein towards the plate-well was observed even in a single culture system of HepG2-NIAS cells with BCLSs put on the plate-well poured a serum-free conditioned medium derived from co-culturing HepG2-NIAS cells with BCLSs and TFK-1 cells. These findings suggest that the culture technology utilizing the crosstalk between HepG2-NIAS cells and TFK-1 cells would provide a new tool for extrapolating the excretion of drug metabolites in the human liver into the bile duct.

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  • Suguru UWAZUMI, Masato NAKAGAWA, Kenzo MORINAGA, Yoshiya HASHIMOTO, Yo ...
    2023 Volume 15 Issue 2 Pages 88-96
    Published: 2023
    Released on J-STAGE: January 19, 2024
    JOURNAL OPEN ACCESS

    Microscopy is a traditional method to estimate the morphology or microstructure of biomaterials. However, the use of stereomicroscopy with transmitted light for the analysis of organic-inorganic composite materials has not been widely explored. In this study, we aimed to verify the usefulness of stereomicroscopy with epi- and trans-illumination and field emission-scanning electron microscopy (FE-SEM) using the bone-substitute material, vacuum-heated epigallocatechin-conjugated gelatin sponges containing β-tricalcium phosphate granules, as model material. Compared with FE-SEM, in situ stereomicroscopy with trans-illumination facilitated the easy observation of the β-tricalcium phosphate granule distribution in sponges. Compared with epi-illumination, transmitted-illumination enabled easy detection of the fibrous structure of epigallocatechin-conjugated gelatin at the intergranular spaces and in the pores of β-tricalcium phosphate granules. Our findings suggest that the use of a stereomicroscope with trans-illumination may facilitate the scanning of the microstructure of organic-inorganic composite materials during biomaterial fabrication.

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  • Takahiro ENDO, Masato NAKAGAWA, Tomonari TANAKA, Yasuhiko MATSUSHIMA, ...
    2023 Volume 15 Issue 2 Pages 97-104
    Published: 2023
    Released on J-STAGE: January 19, 2024
    JOURNAL OPEN ACCESS

    Gelatin-based materials are promising biomaterials for applications in medicine and dentistry. Dehydrothermal treated (vacuum heated) epigallocatechin-conjugated gelatin sponges with or without beta-tricalcium phosphate (β-TCP) granules show greater bone-forming ability than those without this treatment. However, there is a paucity of information associated with the effect of vacuum heating conditions for these materials. In this study, we verified the changes in temperature and time during vacuum heating for the surface topography and viscoelasticity of epigallocatechin-conjugated gelatin sponges with or without β-TCP granules. In scanning electron microscopic observation, there were negligible changes in microstructure or surface topography of epigallocatechin-conjugated gelatin sponges up to 200°C for 4 h or 150°C for 24 h. Meanwhile, in the dynamic viscoelasticity test, the values of the storage and loss moduli remarkably increased beyond 100°C after 4 h heating or extending the heating time up to 16 h at 150°C. This increase was presumably associated with cross-linking in the epigallocatechin-conjugated gelatin. These results offer insights into the use of dehydrothermal treatment with vacuum heating for gelatin-based biomaterials with polyphenols.

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  • Hedele ZENG, Takanori SANO, Jean CACHEUX, Aurélien BANCAUD, Jun-ichi K ...
    2023 Volume 15 Issue 2 Pages 105-111
    Published: 2023
    Released on J-STAGE: January 19, 2024
    JOURNAL OPEN ACCESS

    Mesenchymal stem cells (MSCs) have received attention in the field of regenerative medicine due to their broad-ranging differentiation potential and strong secretory function. Although some studies have shown that MSC transplantation rescues blood flow, its contribution to the repair of microvasculature at the cell-to-tissue level is still obscure. To understand the mechanism of the MSC therapy for ischemic diseases, we developed a three-dimensional (3D) microvessel model cocultured with EphA7+ MSC-like capillary derived pericytes, termed capillary stem cells (CapSCs). It was shown that cocultured CapSCs within the collagen gel matrix tend to accumulate around the microvessel, accompanied with junctional expression VE-cadherin on the endothelial layer. In addition, the barrier function assay showed CapSCs strengthen the endothelial barrier.

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  • Tsubasa SHIRAI, Yasuhiro MATSUDA, Mari NAKAYAMA, Yoshiya HASHIMOTO
    2023 Volume 15 Issue 2 Pages 112-117
    Published: 2023
    Released on J-STAGE: January 19, 2024
    JOURNAL OPEN ACCESS

    Yttria-stabilized zirconia (YSZ) is frequently used for many prostheses, such as implant superstructure. Ceramic materials do not cause problems, such as the elution of metal ions related to corrosion in the oral cavity, differing from metallic materials. Many studies reported the biological properties of zirconia. In addition, its biological safety is relatively high, and its cytotoxicity is weak. However, many studies indicated problems on the biological properties of yttria contained at 2 to 3%. We conducted a cytotoxicity test of yttria powder using a three-dimensional culture method with collagen and cytotoxicity test of yttrium. As a result, the cytotoxicity of these substances was weak, suggesting that this element is not problematic from the viewpoint of cytotoxicity in comparison with metal ions that have been used in the field of dentistry. However, its detailed, multifaceted biological influence should be investigated in the future, considering the inhalation of dust related to dental technology operations and long-term use in the oral cavity for dental purposes.

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