Details of the Researcher

PHOTO

Fan Ziqiu
Section
Graduate School of Dentistry
Job title
Assistant Professor

Research Interests 6

  • Hypertension

  • Oral Biology

  • RBPome

  • Osteocyte

  • Orthodontic tooth movement

  • Post-transcription regulation

Awards 3

  1. Professor Fujino Incentive Award Distinction

    2025/09　Tohoku University

  2. Young Investigator Travel Grant

    2023/09　American Society for Bone and Mineral Research　Azilsartan Inhibits Inflammation-Triggered Bone Resorption and Osteoclastogenesis in vivo via Suppression of TNF-α Expression in Macrophages

  3. Morita Foundation Scholarship

    2022/07　Morita Foundation for Academic Promotion

Papers 19

  1. The Joint Impact of Heavy Metals and Polycyclic Aromatic Hydrocarbons on Periodontitis

    Ziqiu Fan, Guangna Yue, Dongming Yu, Min Zhang, Hideki Kitaura

    International Dental Journal　2025/10

    DOI： 10.1016/j.identj.2025.100879 　

    ISSN： 0020-6539

  2. Transcriptome-Wide Analysis of HuR Function Identifies TXNIP-Mediated Redox Dysregulation in Osteocytes

    Ziqiu Fan, Aseel Marahleh, Hideki Kitaura, Jiayi Ren, Abdulrahman Mousa, Fumitoshi Ohori, Kuniyasu Niizuma, Sherif Rashad, Hiroyasu Kanetaka

    2025/08/08

    DOI： 10.1101/2025.08.08.668956 　

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    <jats:title>Summary</jats:title> <jats:p>Post-transcriptional gene regulation is central to maintaining cellular homeostasis, among its mechanism alternative splicing (AS) fine-tunes cellular adaptation to stress. In this study we employed an approach combining RNA splicing analysis to define RNA binding protein (RBP) motif enrichment around alternatively spliced exons in primary osteocytes cultured in high glucose conditions (HG). We identified the RBP human antigen R (HuR) as a top candidate regulator of AS. Loss of HuR reshaped the transcriptome through widespread changes in gene expression and splicing, converging on two major pathways: stress response and translational control. Functional validation of splicing revealed that HuR depletion heightened oxidative stress sensitivity and compromised cell viability under HG by stabilizing and upregulating TXNIP, a thioredoxin inhibitor. HuR knockdown also impaired mitochondrial mass and function and disrupted key translational signals, despite preserving global protein output. These findings establish HuR as a central post-transcriptional regulator of osteocyte survival and metabolic adaptation under high glucose stress, with potential implications for hyperglycemic bone fragility.</jats:p>

  3. Exacerbating orthodontic tooth movement in mice with salt-sensitive hypertension

    Ziqiu Fan, Hideki Kitaura, Takahiro Noguchi, Fumitoshi Ohori, Aseel Marahleh, Jinghan Ma, Jiayi Ren, Angyi Lin, Kohei Narita, Itaru Mizoguchi

    Journal of Dental Sciences　2025/04

    DOI： 10.1016/j.jds.2024.10.020 　

  4. Azilsartan inhibits inflammation-triggered bone resorption and osteoclastogenesis in vivo via suppression of TNF-α expression in macrophages

    Ziqiu Fan, Hideki Kitaura, Jiayi Ren, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Jinghan Ma, Kayoko Kanou, Mariko Miura, Kohei Narita, Angyi Lin, Itaru Mizoguchi

    Frontiers in Endocrinology　2023/09/15

    DOI： 10.3389/fendo.2023.1207502 　

    ISSN： 1664-2392

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    <jats:sec><jats:title>Introduction</jats:title><jats:p>Hypertension is a major risk factor for cardiovascular disease (CVD) and is associated with increased bone loss due to excessive activity of the local renin-angiotensin system (RAS). Angiotensinogen/Angiotensin (ANG) II/Angiotensin II type 1 receptor (AT1R) axis is considered as the core axis regulating RAS activity. Azilsartan is an FDA-approved selective AT1R antagonist that is used to treat hypertension. This study aimed to determine whether azilsartan affects formation of osteoclast, resorption of bone, and the expression of cytokines linked with osteoclastogenesis during lipopolysaccharide (LPS)-triggered inflammation <jats:italic>in vivo</jats:italic>.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p><jats:italic>In vivo</jats:italic>, following a 5-day supracalvarial injection of LPS or tumor necrosis factor-alpha (TNF-α) with or without azilsartan, the proportion of bone resorption and the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, which are identified as osteoclasts on mice calvariae were counted. The mRNA expression levels of TRAP, cathepsin K, receptor activator of NF-κB ligand (RANKL), and TNF-α were also evaluated. <jats:italic>In vitro</jats:italic>, the effect of azilsartan (0, 0.01, 0.1, 1, and 10 μM) on RANKL and TNF-α-triggered osteoclastogenesis were investigated. Also, whether azilsartan restrains LPS-triggered TNF-α mRNA and protein expression in macrophages and RANKL expression in osteoblasts were assessed. Furthermore, western blotting for analysis of mitogen-activated protein kinases (MAPKs) signaling was conducted.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Azilsartan-treated calvariae exhibited significantly lower bone resorption and osteoclastogenesis than those treated with LPS alone. <jats:italic>In vivo</jats:italic>, LPS with azilsartan administration resulted in lower levels of receptor activator of RANKL and TNF-α mRNA expression than LPS administration alone. Nevertheless, azilsartan did not show inhibitory effect on RANKL- and TNF-α-triggered osteoclastogenesis <jats:italic>in vitro</jats:italic>. Compared to macrophages treated with LPS, TNF-α mRNA and protein levels were lower in macrophages treated by LPS with azilsartan. In contrast, RANKL mRNA and protein expression levels in osteoblasts were the same in cells co-treated with azilsartan and LPS and those exposed to LPS only. Furthermore, azilsartan suppressed LPS-triggered MAPKs signaling pathway in macrophages. After 5-day supracalvarial injection, there is no difference between TNF-α injection group and TNF-α with azilsartan injection group.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These findings imply that azilsartan prevents LPS-triggered TNF-α production in macrophages, which in turn prevents LPS-Triggered osteoclast formation and bone resorption <jats:italic>in vivo</jats:italic>.</jats:p></jats:sec>

  5. Liraglutide, a GLP-1 Receptor Agonist, Mitigates LPS-Induced Osteoclastogenesis and Bone Loss by Downregulating Macrophage TNF-α Expression

    Kou Murakami, Hideki Kitaura, Fumitoshi Ohori, Aseel Marahleh, Angyi Lin, Ziqiu Fan, Kohei Narita, Tomoko Ishiyama, Jin Hu, Huidan Zheng, Hiroyasu Kanetaka

    International Journal of Molecular Sciences　2026/06/22

    DOI： 10.3390/ijms27125624 　

  6. Cell Death in Orthodontic Tooth Movement: Recent Advances and Emerging Insights

    Fumitoshi Ohori, Hideki Kitaura, Aseel Marahleh, Jinghan Ma, Kohei Narita, Angyi Lin, Ziqiu Fan, Kou Murakami, Hiroyasu Kanetaka

    International Journal of Molecular Sciences　2026/01/22

    DOI： 10.3390/ijms27021130 　

  7. The Role of Glucose-Dependent Insulinotropic Polypeptide (GIP) in Bone Metabolism

    Angyi Lin, Hideki Kitaura, Fumitoshi Ohori, Aseel Marahleh, Jinghan Ma, Ziqiu Fan, Kohei Narita, Kou Murakami, Hiroyasu Kanetaka

    International Journal of Molecular Sciences　2026/01/07

    DOI： 10.3390/ijms27020600 　

  8. Lipocalin-2 upregulation in hypoxic murine osteocytes enhances RANKL-induced osteoclastogenesis

    Kohei Narita, Fumitoshi Ohori, Aseel Marahleh, Jinghan Ma, Jiayi Ren, Angyi Lin, Ziqiu Fan, Kou Murakami, Hideki Kitaura

    Scientific Reports　2026/01/06

    DOI： 10.1038/s41598-025-34575-2 　

    ISSN： 2045-2322

  9. HuR Knockdown in MLO-Y4 Osteocyte-like Cells Elevates OPG Expression and Suppresses Osteoclastogenesis In Vitro

    Ziqiu Fan, Hideki Kitaura, Aseel Marahleh, Abdulrahman Mousa, Fumitoshi Ohori, Alexandru Craevschi, Sherif Rashad, Hiroyasu Kanetaka

    International Journal of Molecular Sciences　2025/12/31

    DOI： 10.3390/ijms27010430 　

  10. Rewiring of RNA–protein coupling in osteocytes in response to hyperglycemic levels of glucose

    Aseel Marahleh, Sherif Rashad, Eisuke Kanao, Ziqiu Fan, Fumitoshi Ohori, Hideki Kitaura

    2025/12/25

    DOI： 10.64898/2025.12.25.696466 　

  11. (D-Ala2)GIP Inhibits TNF-α-Induced Osteoclast Formation and Bone Resorption, and Orthodontic Tooth Movement

    Angyi Lin, Hideki Kitaura, Jinghan Ma, Fumitoshi Ohori, Aseel Marahleh, Kayoko Kanou, Kohei Narita, Ziqiu Fan, Kou Murakami, Hiroyasu Kanetaka

    International Journal of Molecular Sciences　2025/12/24

    DOI： 10.3390/ijms27010199 　

  12. Recent Advances in the Role of Osteocytes in Orthodontic Tooth Movement

    Aseel Marahleh, Fumitoshi Ohori, Jinghan Ma, Ziqiu Fan, Angyi Lin, Kohei Narita, Kou Murakami, Hideki Kitaura

    International Journal of Molecular Sciences　2025/09/26

    DOI： 10.3390/ijms26199396 　

  13. Docosahexaenoic Acid Inhibits Osteoclastogenesis via FFAR4-Mediated Regulation of Inflammatory Cytokines

    Jinghan Ma, Hideki Kitaura, Fumitoshi Ohori, Aseel Marahleh, Ziqiu Fan, Angyi Lin, Kohei Narita, Kou Murakami, Hiroyasu Kanetaka

    Molecules　2025/07/29

    DOI： 10.3390/molecules30153180 　

  14. Evaluation of the effects for root resorption in orthodontic tooth movement with micro-osteoperforations in mice

    Ndemuweda, T., Kitaura, H., Ohori, F., Marahleh, A., Ma, J., Fan, Z., Lin, A., Narita, K., Itou, A., Mizoguchi, I.

    Journal of Dental Sciences　20　(3)　2025/07

    DOI： 10.1016/j.jds.2025.02.017 　

    ISSN： 1991-7902 2213-8862

  15. Osteocyte necroptosis drives osteoclastogenesis and alveolar bone resorption during orthodontic tooth movement

    Ohori, F., Kitaura, H., Marahleh, A., Ma, J., Miura, M., Ren, J., Narita, K., Fan, Z., Lin, A., Mizoguchi, I.

    Scientific Reports　15　(1)　2025/06/03

    DOI： 10.1038/s41598-025-04697-8 　

    ISSN： 2045-2322

  16. Angiotensin II Promotes Osteocyte RANKL Expression via AT1R Activation

    Jiayi Ren, Aseel Marahleh, Jinghan Ma, Fumitoshi Ohori, Takahiro Noguchi, Ziqiu Fan, Jin Hu, Kohei Narita, Angyi Lin, Hideki Kitaura

    Biomedicines　2025/02/10

    DOI： 10.3390/biomedicines13020426 　

  17. Role of CXCL10 released from osteocytes in response to TNF-α stimulation on osteoclasts

    Miura, M., Kitaura, H., Ohori, F., Narita, K., Ren, J., Noguchi, T., Marahleh, A., Ma, J., Lin, A., Fan, Z., Mizoguchi, I.

    Scientific Reports　15　(1)　2025/01/24

    DOI： 10.1038/s41598-025-87092-7 　

    ISSN： 2045-2322

  18. (D-Ala2)GIP Inhibits Inflammatory Bone Resorption by Suppressing TNF-α and RANKL Expression and Directly Impeding Osteoclast Formation

    Angyi Lin, Hideki Kitaura, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Jinghan Ma, Jiayi Ren, Mariko Miura, Ziqiu Fan, Kohei Narita, Itaru Mizoguchi

    International Journal of Molecular Sciences　2024/02/22

    DOI： 10.3390/ijms25052555 　

  19. Exogenous Angiotensin-(1–7) Provides Protection Against Inflammatory Bone Resorption and Osteoclastogenesis by Inhibition of TNF-α Expression in Macrophages

    Ren, J., Kitaura, H., Noguchi, T., Ohori, F., Marahleh, A., Ma, J., Kanou, K., Fan, Z., Mizoguchi, I.

    Calcified Tissue International　115　(4)　2024

    DOI： 10.1007/s00223-024-01257-6 　

    ISSN： 0171-967X 1432-0827

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Research Projects 1

  1. Pioneering Research Support Project

    Offer Organization: Japan Science and Technology Agency

    2022/04 - 2026/03