Alexidine Dihydrochloride Attenuates Osteoclast Formation and Bone Resorption and Protects Against LPS-Induced Osteolysis

作者：Zhu, Xiang; Gao, Junjie; Ng, Pei Y.; Qin, An; Steer, James H.; Pavlos, Nathan J.; Zheng, Ming H.; Dong, Yang; Cheng, Tak S.^*

来源：Journal of Bone and Mineral Research, 2016, 31(3): 560-572.

DOI：10.1002/jbmr.2710

• ALEXIDINE DIHYDROCHLORIDE
• OSTEOLYSIS
• OSTEOCLAST
• BONE RESORPTION
• MAPK AND NFATc1 SIGNALING PATHWAYS

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-B 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.

• 出版日期2016-3
• 单位上海交通大学