The Inhibition of RANKL-Induced Osteoclastogenesis through the Suppression of p38 Signaling Pathway by Naringenin and Attenuation of Titanium-Particle-Induced Osteolysis

International Journal of Molecular Sciences

Wengang Wang¹  Chuanlong Wu¹  Bo Tian¹  Xuqiang Liu¹  Zanjing Zhai¹  Xinhua Qu¹  Chuan Jiang¹  Zhengxiao Ouyang¹  Yuanqing Mao¹  Tingting Tang¹  An Qin¹  Zhenan Zhu¹ 

[1] Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; E-Mails:

关键词: naringenin;    osteolysis;    osteoclast;    p38 signaling;    NFATc1;   

DOI  :  10.3390/ijms151221913

来源: mdpi

【 摘 要 】

The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic loosening is most likely due to increased bone resorption by osteoclasts. Through in vitro studies, we demonstrated that naringenin, a naturally occurring flavanone in grapefruit and tomatoes, exerts potent inhibitory effects on the ligand of the receptor activator of nuclear factor-κB (RANKL)-induced osteoclastogenesis and revealed that the mechanism of action of naringenin, which inhibited osteoclastogenesis by suppression of the p38 signaling pathway. Through in vivo studies, we proved that naringenin attenuated titanium particle-induced osteolysis in a mouse calvarial model. In general, we demonstrated that naringenin inhibited osteoclastogenesis via suppression of p38 signaling in vitro and attenuated titanium particle-induced osteolysis in vivo. This study also suggested that naringenin has significant potential for the treatment of osteolysis-related diseases caused by excessive osteoclast formation and activity.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.