2. Academic Validation
  3. 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

  • Biochem Pharmacol. 2016 Mar 15;104:118-30. doi: 10.1016/j.bcp.2016.02.013.
Xiang Zhu 1,  Jun J Gao 2,  Euphemie Landao-Bassonga 2,  Nathan J Pavlos 2,  An Qin 3,  James H Steer 4,  Ming H Zheng 2,  Yang Dong 5,  Tak S Cheng 6
Affiliations

Affiliations

  • 1 Centre for Orthopaedic Research, School of Surgery, University of Western Australia, Crawley, Western Australia 6009, Australia; Department of Orthopaedics, Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
  • 2 Centre for Orthopaedic Research, School of Surgery, University of Western Australia, Crawley, Western Australia 6009, Australia.
  • 3 Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
  • 4 Pharmacology Unit, School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia 6009, Australia.
  • 5 Department of Orthopaedics, Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China. Electronic address: [email protected].
  • 6 Centre for Orthopaedic Research, School of Surgery, University of Western Australia, Crawley, Western Australia 6009, Australia. Electronic address: [email protected].
PMID: 26906912 DOI: 10.1016/j.bcp.2016.02.013
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.

Keywords

Concanamycin A (PubChem CID: 3649143); NF-κB; NFATc1; Nigericin (PubChem CID: 34230); Osteoclast; Osteolysis; Thonzonium bromide; Thonzonium bromide (PubChem CID: 11102); Valinomycin (PubChem CID: 5649).

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