Alexidine dihydrochloride attenuates osteoclast formation and bone resorption and protects against LPS-induced osteolysis

Xiang Zhu, Junjie Gao, Pei Ying Ng, A Qin, Jay Steer, Nathan Pavlos, Minghao Zheng, Y. Dong, Tak Sum Cheng

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Aseptic loosening and periprosthetic infection leading to inflammatory osteolysis is a major complication associated with total joint arthroplasty (TJA). The liberation of bacterial products and/or implant-derived wear particles activates immune cells that produce pro-osteoclastogenic cytokines that enhance osteoclast recruitment and activity, leading to bone destruction and osteolysis. Therefore, agents that prevent the inflammatory response and/or attenuate excessive osteoclast (OC) formation and bone resorption offer therapeutic potential by prolonging the life of TJA implants. Alexidine dihydrochloride (AD) is a bisbiguanide compound commonly used as an oral disinfectant and in contact lens solutions. It possesses antimicrobial, anti-inflammatory and anticancer properties; however, its effects on OC biology are poorly described. Here, we demonstrate that AD inhibits OC formation and bone resorption in vitro and exert prophylatic protection against LPS-induced osteolysis in vivo. Biochemical analysis demonstrated that AD suppressed receptor activator of NF-κB ligand (RANKL)-induced activation of mitogen-activated protein kinases (ERK, p38, and JNK), leading to the downregulation of NFATc1. Furthermore, AD disrupted F-actin ring formation and attenuated the ability of mature OC to resorb bone. Collectively, our findings suggest that AD may be a promising prophylactic anti-osteoclastic/resorptive agent for the treatment of osteolytic diseases caused by excessive OC formation and function. © 2015 American Society for Bone and Mineral Research.
Original languageEnglish
Pages (from-to)560-572
Number of pages13
JournalJournal of Bone & Mineral Research
Volume31
Issue number3
Early online date6 Jan 2016
DOIs
Publication statusPublished - 16 Mar 2016

Fingerprint Dive into the research topics of 'Alexidine dihydrochloride attenuates osteoclast formation and bone resorption and protects against LPS-induced osteolysis'. Together they form a unique fingerprint.

Cite this