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

13 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

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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}",
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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

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SP - 118

EP - 130

JO - Journal of Biochemical Pharmacology

JF - Journal of Biochemical Pharmacology

SN - 0006-2952

ER -