Biomedical Research
Online ISSN : 1880-313X
Print ISSN : 0388-6107
ISSN-L : 0388-6107
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Showing 1-6 articles out of 6 articles from the selected issue
Review
  • Tomomaya YAMAMOTO, Tomoka HASEGAWA, Paulo Henrique Luiz de FRAITAS, Hi ...
    Type: research-article
    2021 Volume 42 Issue 5 Pages 161-171
    Published: September 21, 2021
    Released: September 21, 2021
    JOURNAL FREE ACCESS

    Modeling, the changes of bone size and shape, often takes place at the developmental stages, whereas bone remodeling—replacing old bone with new bone—predominantly occurs in adults. Unlike bone remodeling, bone formation induced by modeling i.e., minimodeling (microscopic modeling in cancellous bone) is independent of osteoclastic bone resorption. Although recently-developed drugs for osteoporotic treatment could induce minimodeling-based bone formation in addition to remodeling-based bone formation, few reports have demonstrated the histological aspects of minimodeling-based bone formation. After administration of eldecalcitol or romosozumab, unlike teriparatide treatment, mature osteoblasts formed new bone by minimodeling, without developing thick preosteoblastic layers. The histological characteristics of minimodeling-based bone formation is quite different from remodeling, as it is not related to osteoclastic bone resorption, resulting in convex-shaped new bone and smooth cement lines called arrest lines. In this review, we will show histological properties of minimodeling-based bone formation by osteoporotic drugs.

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Full Papers
  • Kazuyoshi TAKEDA, Ko OKUMURA
    Type: research-article
    2021 Volume 42 Issue 5 Pages 173-179
    Published: September 21, 2021
    Released: September 21, 2021
    JOURNAL FREE ACCESS

    Nicotinamide mononucleotide (NMN), a key nicotinamide adenine dinucleotide (NAD+) intermediate, has been shown to ameliorate various pathologies in elderly mouse disease models. Natural killer (NK) cells are important innate immune cells; however, their functions decline with aging. In this study, we examined the effect of NMN treatment on NK cells in mice. Intraperitoneal administration of NMN augmented NK cell cytotoxic activity in both young and elderly B6 mice as well as young BALB/c mice. Oral administration of NMN also increased NK cell cytotoxicity in elderly B6 and BALB/c mice. However, the NK cell population was not increased in the mice whose NK cell cytotoxic activity was activated by NMN. Interestingly, NMN administration did not augment NK cell cytotoxic activity in IFN-γ deficient mice. These results suggest that NMN administration augments NK cell cytotoxic activity, but not cell number, in a manner dependent on IFN-γ in both young and elderly mice.

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  • Satoshi TSUZUKI, Yusaku KIMOTO, Masayuki YAMASAKI, Tatsuya SUGAWARA, Y ...
    Type: research-article
    2021 Volume 42 Issue 5 Pages 181-191
    Published: September 21, 2021
    Released: September 21, 2021
    JOURNAL FREE ACCESS

    Cluster of differentiation 36 (CD36) is a cell-surface receptor that recognizes diverse substances. We have presented indirect evidence that a short segment of the receptor comprising amino acids 149–168 contains a site for binding of its lipid ligands (e.g., distinct fatty acids and aldehydes). However, experimental support for their direct interactions is yet to be achieved. For this, we devised a fluorescence intensity assay, where a synthetic peptide consisting of CD36 amino acids 149–168 labeled with fluorescein isothiocyanate (FITC-CD36149–168) and its variant peptides were used as positive and negative probes, respectively. First, we obtained results indicating that 1-palmitoyl-2-(5-keto-6-octenedioyl)phosphatidylcholine (an established CD36 ligand) but not 1-palmitoyl-2-arachidonyl-phosphatidylcholine (a non-ligand of the receptor) bound in a saturable and specific manner to FITC-CD36149–168. Strikingly, the assay allowed us to provide the first evidence supporting direct and specific binding between the CD36 segment and fatty aldehydes (e.g., Z-11-hexadecenal). However, this method failed to illustrate specific interactions of the segment with fatty acids, such as oleic acid. Nonetheless, our findings offer further insight into the biologically relevant ligands and the role of CD36. In addition, we suggest that this fluorescence-based technique provides a convenient means to evaluate protein (peptide)-lipid interactions.

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  • Narumi ISHIDA, Kaori MURATA, Takao MORITA, Shingo SEMBA, Akihiro NEZU, ...
    Type: research-article
    2021 Volume 42 Issue 5 Pages 193-201
    Published: September 21, 2021
    Released: September 21, 2021
    JOURNAL FREE ACCESS

    Genetically-encoded calcium indicators such as G-GECO are useful for studying Ca2+ responses during long-term processes. In this study, we employed a lentiviral vector and established a rat dental epithelial cell line that stably expressed G-GECO (SF2-G-GECO). Ca2+ imaging analysis under cell culture conditions revealed that SF2-G-GECO cells exhibited spontaneous Ca2+ responses, which could be classified into the following three major patterns depending on the cell density: localized Ca2+ responses at cell protrusions at a low density, a cell-wide spread of Ca2+ responses at a medium density, and Ca2+ responses in clusters of 3–20 cells at a high density. The P2Y receptor inhibitor suramin (10 μM), the ATP-degrading enzyme apyrase (5 units/mL), and the fibroblast growth factor (FGF) receptor inhibitor FIIN-2 (1 μM) decreased the frequency of spontaneous Ca2+ responses. These results indicate that ATP and FGF are involved in the spontaneous Ca2+ responses. SF2 cells differentiate into ameloblasts via interactions with mesenchymal cells. Therefore, SF2-G-GECO cells are expected to be a useful tool for studying the functions of Ca2+ responses in regulating gene expression during tooth development.

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  • Manuel Alejandro CAMPOS MEDINA, Kenji IEMURA, Akatsuki KIMURA, Kozo TA ...
    Type: research-article
    2021 Volume 42 Issue 5 Pages 203-219
    Published: September 21, 2021
    Released: September 21, 2021
    JOURNAL FREE ACCESS
    Supplementary material

    Chromosome oscillation during metaphase is attenuated in cancer cell lines, concomitant with the reduction of Aurora A activity on kinetochores, which results in reduced mitotic fidelity. To verify the correlation between Aurora A activity, chromosome oscillation, and error correction efficiency, we developed a mathematical model of kinetochore-microtubule dynamics, based on stochastic attachment/detachment events regulated by Aurora A activity gradient centered at spindle poles. The model accurately reproduced the oscillatory movements of chromosomes, which were suppressed not only when Aurora A activity was inhibited, but also when it was upregulated, mimicking the situation in cancer cells. Our simulation also predicted efficient correction of erroneous attachments through chromosome oscillation, which was hampered by both inhibition and upregulation of Aurora A activity. Our model provides a framework to understand the physiological role of chromosome oscillation in the correction of erroneous attachments that is intrinsically related to Aurora A activity.

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Communication
  • Dan YANG, Hideaki OIKE, Mitsuhiro FURUSE, Shinobu YASUO
    Type: research-article
    2021 Volume 42 Issue 5 Pages 221-227
    Published: September 21, 2021
    Released: September 21, 2021
    JOURNAL FREE ACCESS

    Irregular light-dark cycles desynchronize the circadian clock via hormonal and neuronal pathways and increase the risk of various diseases. This study demonstrated that a single pulse of spermidine—a polyamine—strongly induced circadian phase advances in the presence or absence of dexamethasone (a synthetic glucocorticoid) in NIH3T3 cells transfected with the Bmal1 promotor-driven luciferase reporter gene. The spermidine-induced phase advances were 2–3 fold greater than were the dexamethasone-induced shifts. The phase resetting effect of spermidine occurred in a dose- and time-dependent manner and was not blocked by RU486, an antagonist of glucocorticoid receptors. Spermidine treatment modulated the expression of clock genes within 60 min, which was sooner than changes in the expression of autophagy-related genes. These findings suggested that spermidine is a potent modulator of the circadian phase, acting through glucocorticoid receptor-independent pathways, and may be useful for treating diseases related to circadian desynchrony.

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