The effect of enoxacin on osteoclastogenesis and reduction of titanium particle-induced osteolysis via suppression of JNK signaling pathway

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• 作者：Xuqiang Liu^a ; ¹ ; Xinhua Qu^a ; ¹ ; Chuanlong Wu^a ; ¹ ; Zanjing Zhai^a ; ¹ ; Bo Tian^a ; Haowei Li^a ; Zhengxiao Ouyang^a ; ^b ; Xinchen Xu^c ; Wengang Wang^a ; Qiming Fan^a ; Tingting Tang^a ; An Qin^a ; ^{dr.qinan@gmail.com" class="auth_mail} ; Kerong Dai^a ; ^{daikerong12000@163.com" class="auth_mail} ; ^{krdai@163.com" class="auth_mail} ; ^{krdai@sibs.ac.cn" class="auth_mail}
• 关键词：Enoxacin ; Prosthetic loosening ; Osteolysis ; Osteoclasts ; JNK signaling
• 刊名：Biomaterials
• 出版年：July 2014
• 年：2014
• 卷：35
• 期：22
• 页码：5721-5730
• 全文大小：3718 K

文摘

The aim of this study was to assess the effect of enoxacin on osteoclastogenesis and titanium particle-induced osteolysis. Wear particles liberated from the surface of prostheses are associated with aseptic prosthetic loosening. It is well established that wear particles induce inflammation, and that extensive osteoclastogenesis plays a critical role in peri-implant osteolysis and subsequent prosthetic loosening. Therefore, inhibiting extensive osteoclast formation and bone resorption could be a potential therapeutic target to prevent prosthetic loosening. In this study, we demonstrated that enoxacin, a fluoroquinolone antibiotic, exerts potent inhibitory effects on titanium particle-induced osteolysis in a mouse calvarial model. Interestingly, the number of mature osteoclasts decreased after treatment with enoxacin in vivo, suggesting that osteoclast formation might be inhibited by enoxacin. We then performed in vitro studies to confirm our hypothesis and revealed the mechanism of action of enoxacin. Enoxacin inhibited osteoclast formation by specifically abrogating RANKL-induced JNK signaling. Collectively, these results suggest that enoxacin, an antibiotic with few side effects that is widely used in clinics, had significant potential for the treatment of particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function.