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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01053

Stevioside prevents wear particle-induced osteolysis by inhibiting osteoclastogenesis and inflammatory response via the suppression of TAK1 activation

 Jiahong Meng1*,  Chen-he Zhou1, Bin Hu1, Mengmeng Luo2, Haobo Wu1, Yute Yang1, Yangxin Wang1, Guangyao Jiang1,  Jianqiao Hong1, Sihao Li1 and Weiqi Yan1
  • 1Second Affiliated Hospital, Zhejiang University School of Medicine, China
  • 2First Affiliated Hospital, College of Medicine, Zhejiang University, China

Aseptic loosening and periprosthetic osteolysis are the leading causes of total joint arthroplasty failure, which occurs as a result of chronic inflammatory response and enhanced osteoclast activity. Here we showed that stevioside, a natural compound isolated from Stevia rebaudiana, exhibited preventative effects on titanium particle-induced osteolysis in a mouse calvarial model. Further histological assessment and real-time PCR analysis indicated that stevioside prevented titanium particle-induced osteolysis by inhibiting osteoclast formation and inflammatory cytokine expression in vivo. In vitro, we found that stevioside could suppress RANKL-induced osteoclastogenesis and titanium particle-induced inflammatory response in a dose-dependent manner. Mechanistically, stevioside achieved these effects by disrupting the phosphorylation of TAK1 and subsequent activation of NF-κB/MAPKs signaling pathways. Collectively, our data suggest that stevioside effectively suppresses osteoclastogenesis and inflammatory response both in vitro and in vivo, and it might be a potential therapy for particle-induced osteolysis and other osteolytic diseases.

Keywords: Aseptic loosening, osteoclast, NF-κB – nuclear factor-kappa B, MAPK, TAK1

Received: 26 Jun 2018; Accepted: 31 Aug 2018.

Edited by:

Viktória Jeney, University of Debrecen, Hungary

Reviewed by:

David M. Findlay, University of Adelaide, Australia
Teun J. De Vries, Academic Centre for Dentistry Amsterdam (ACTA), VU University Amsterdam, Netherlands  

Copyright: © 2018 Meng, Zhou, Hu, Luo, Wu, Yang, Wang, Jiang, Hong, Li and Yan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jiahong Meng, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China,