The effect of enoxacin on osteoclastogenesis and reduction of titanium particle-induced osteolysis via suppression of JNK signaling pathway.
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.
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Xuqiang
X
Liu
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Xinhua
X
Qu
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Chuanlong
C
Wu
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Zanjing
Z
Zhai
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Bo
B
Tian
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Haowei
H
Li
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Zhengxiao
Z
Ouyang
College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xinchen
X
Xu
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Wengang
W
Wang
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Qiming
Q
Fan
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Tingting
T
Tang
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: dr.qinan@gmail.com.
An
A
Qin
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: daikerong12000@163.com.
Kerong
K
Dai
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002460:Cell Line; D015365:Enoxacin / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010014:Osteolysis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D019736:Prostheses and Implants / Q000009:adverse effects; D014025:Titanium / Q000009:adverse effects*
D000890:Anti-Infective Agents; D015365:Enoxacin; D014025:Titanium
Enoxacin; JNK signaling; Osteoclasts; Osteolysis; Prosthetic loosening