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

16 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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