Thonzonium bromide inhibits RANKL-induced osteoclast formation and bone resorption in vitro and prevents LPS-induced bone loss in vivo

Xiang Zhu, Junjie Gao, Euphemie Landao-Bassonga, Nathan Pavlos, A. Qin, Jay Steer, Minghao Zheng, Y. Dong, Tak Sum Cheng

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    Crown Copyright © 2016 Published by Elsevier Inc. All rights reserved. Osteoclasts (OCs) play a pivotal role in a variety of lytic bone diseases including osteoporosis, arthritis, bone tumors, Paget's disease and the aseptic loosening of orthopedic implants. The primary focus for the development of bone-protective therapies in these diseases has centered on the suppression of OC formation and function. In this study we report that thonzonium bromide (TB), a monocationic surface-active agent, inhibited RANKL-induced OC formation, the appearance of OC-specific marker genes and bone-resorbing activity in vitro. Mechanistically, TB blocked the RANKL-induced activation of NF-?B, ERK and c-Fos as well as the induction of NFATc1 which is essential for OC formation. TB disrupted F-actin ring formation resulting in disturbances in cytoskeletal structure in mature OCs during bone resorption. Furthermore, TB exhibited protective effects in an in vivo murine model of LPS-induced calvarial osteolysis. Collectively, these data suggest that TB might be a useful alternative therapy in preventing or treating osteolytic diseases.
    Original languageEnglish
    Pages (from-to)118-130
    Number of pages13
    JournalBiochemical Pharmacology
    Volume104
    Early online date21 Feb 2016
    DOIs
    Publication statusPublished - 15 Mar 2016

    Fingerprint

    Osteoclasts
    Bone Resorption
    Bromides
    Bone
    Bone and Bones
    Osteitis Deformans
    Osteolysis
    Bone Diseases
    Bone Development
    Orthopedics
    Complementary Therapies
    Crowns
    Surface-Active Agents
    Osteoporosis
    Arthritis
    thonzonium bromide
    In Vitro Techniques
    Actins
    Tumors
    Genes

    Cite this

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    title = "Thonzonium bromide inhibits RANKL-induced osteoclast formation and bone resorption in vitro and prevents LPS-induced bone loss in vivo",
    abstract = "Crown Copyright {\circledC} 2016 Published by Elsevier Inc. All rights reserved. Osteoclasts (OCs) play a pivotal role in a variety of lytic bone diseases including osteoporosis, arthritis, bone tumors, Paget's disease and the aseptic loosening of orthopedic implants. The primary focus for the development of bone-protective therapies in these diseases has centered on the suppression of OC formation and function. In this study we report that thonzonium bromide (TB), a monocationic surface-active agent, inhibited RANKL-induced OC formation, the appearance of OC-specific marker genes and bone-resorbing activity in vitro. Mechanistically, TB blocked the RANKL-induced activation of NF-?B, ERK and c-Fos as well as the induction of NFATc1 which is essential for OC formation. TB disrupted F-actin ring formation resulting in disturbances in cytoskeletal structure in mature OCs during bone resorption. Furthermore, TB exhibited protective effects in an in vivo murine model of LPS-induced calvarial osteolysis. Collectively, these data suggest that TB might be a useful alternative therapy in preventing or treating osteolytic diseases.",
    author = "Xiang Zhu and Junjie Gao and Euphemie Landao-Bassonga and Nathan Pavlos and A. Qin and Jay Steer and Minghao Zheng and Y. Dong and Cheng, {Tak Sum}",
    year = "2016",
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    language = "English",
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    TY - JOUR

    T1 - Thonzonium bromide inhibits RANKL-induced osteoclast formation and bone resorption in vitro and prevents LPS-induced bone loss in vivo

    AU - Zhu, Xiang

    AU - Gao, Junjie

    AU - Landao-Bassonga, Euphemie

    AU - Pavlos, Nathan

    AU - Qin, A.

    AU - Steer, Jay

    AU - Zheng, Minghao

    AU - Dong, Y.

    AU - Cheng, Tak Sum

    PY - 2016/3/15

    Y1 - 2016/3/15

    N2 - Crown Copyright © 2016 Published by Elsevier Inc. All rights reserved. Osteoclasts (OCs) play a pivotal role in a variety of lytic bone diseases including osteoporosis, arthritis, bone tumors, Paget's disease and the aseptic loosening of orthopedic implants. The primary focus for the development of bone-protective therapies in these diseases has centered on the suppression of OC formation and function. In this study we report that thonzonium bromide (TB), a monocationic surface-active agent, inhibited RANKL-induced OC formation, the appearance of OC-specific marker genes and bone-resorbing activity in vitro. Mechanistically, TB blocked the RANKL-induced activation of NF-?B, ERK and c-Fos as well as the induction of NFATc1 which is essential for OC formation. TB disrupted F-actin ring formation resulting in disturbances in cytoskeletal structure in mature OCs during bone resorption. Furthermore, TB exhibited protective effects in an in vivo murine model of LPS-induced calvarial osteolysis. Collectively, these data suggest that TB might be a useful alternative therapy in preventing or treating osteolytic diseases.

    AB - Crown Copyright © 2016 Published by Elsevier Inc. All rights reserved. Osteoclasts (OCs) play a pivotal role in a variety of lytic bone diseases including osteoporosis, arthritis, bone tumors, Paget's disease and the aseptic loosening of orthopedic implants. The primary focus for the development of bone-protective therapies in these diseases has centered on the suppression of OC formation and function. In this study we report that thonzonium bromide (TB), a monocationic surface-active agent, inhibited RANKL-induced OC formation, the appearance of OC-specific marker genes and bone-resorbing activity in vitro. Mechanistically, TB blocked the RANKL-induced activation of NF-?B, ERK and c-Fos as well as the induction of NFATc1 which is essential for OC formation. TB disrupted F-actin ring formation resulting in disturbances in cytoskeletal structure in mature OCs during bone resorption. Furthermore, TB exhibited protective effects in an in vivo murine model of LPS-induced calvarial osteolysis. Collectively, these data suggest that TB might be a useful alternative therapy in preventing or treating osteolytic diseases.

    U2 - 10.1016/j.bcp.2016.02.013

    DO - 10.1016/j.bcp.2016.02.013

    M3 - Article

    VL - 104

    SP - 118

    EP - 130

    JO - Journal of Biochemical Pharmacology

    JF - Journal of Biochemical Pharmacology

    SN - 0006-2952

    ER -