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Thonzonium Bromide Inhibits RANKL-induced Osteoclast Formation and Bone Resorption in Vitro and Prevents LPS-induced Bone Loss in Vivo

Thonzonium Bromide Inhibits RANKL-induced Osteoclast Formation and Bone Resorption in Vitro and Prevents LPS-induced Bone Loss in Vivo

Xiang Zhu, Jun J Gao, Euphemie Landao-Bassonga, Nathan J Pavlos, An Qin, James H Steer, Ming H Zheng, Yang Dong, Tak S Cheng

Biochem Pharmacol. 2016 Mar 15;104:118-30.

PMID: 26906912

Abstract:

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-κB, 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP553082	Thonzonium bromide		553-08-2	Price

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