期刊
JOURNAL OF BONE AND MINERAL RESEARCH
卷 31, 期 3, 页码 560-572出版社
WILEY-BLACKWELL
DOI: 10.1002/jbmr.2710
关键词
ALEXIDINE DIHYDROCHLORIDE; OSTEOLYSIS; OSTEOCLAST; BONE RESORPTION; MAPK AND NFATc1 SIGNALING PATHWAYS
资金
- Australian National Health and Medical Research Council (NH&MRC) Project Grant [APP1049884]
- National Natural Science Foundation of China [81328015]
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. (c) 2015 American Society for Bone and Mineral Research.
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