文献类型：期刊文献

英文题名：Inhibition of osteolysis after local administration of osthole in a TCP particles-induced osteolysis model

作者：Lv, Shumin[1];Zhang, Yun[1];Yan, Ming[2];Mao, Hongjiao[1];Pan, Cailing[1];Gan, Mingxiao[1];Fan, Jiawen[1];Wang, Guoxia[1]

机构：[1]Shaoxing Univ, Coll Med, Huancheng West Rd 508, Shaoxing 312000, Peoples R China;[2]Hangzhou Dianzi Univ, Coll Life Informat Sci & Instrument Engn, Hangzhou 310018, Zhejiang, Peoples R China

年份：2016

卷号：40

期号：7

起止页码：1545

外文期刊名：INTERNATIONAL ORTHOPAEDICS

收录：SCI-EXPANDED(收录号：WOS:000379028900028)、、Scopus(收录号：2-s2.0-84945258968)、WOS

基金：This work was supported by Zhejiang Provincial Natural Science Foundation of China (No. LY13H060003 and No. LY15H180012), Scientific Research Foundation of Traditional Chinese Medicine in Zhejiang Province (No.2012ZB161) and Science & Technology Innovation Project of College Students in Zhejiang Province (No. 2013R426025).

语种：英文

外文关键词：TCP particles; Osteolysis; Osthole; ER stress

外文摘要：Purpose Wear debris-induced osteolysis and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. However, no effective measures for the prevention and treatment of particles-induced osteolysis currently exist. Here, we investigated the efficacy of local administration of osthole on tricalcium phosphate (TCP) particles-induced osteolysis in a murine calvarial model. Methods TCP particles were implanted over the calvaria of ICR mice, and established TCP particles-induced osteolysis model. On days one, four, seven, ten and thirteen post-surgery, osthole (10 mg/kg) or phosphate buffer saline (PBS) were subcutaneously injected into the calvaria of TCP particles-implanted or sham-operated mice. Two weeks later, blood, the periosteum and the calvaria were collected and processed for bone turnover markers, pro-inflammatory cytokine, histomorphometric and molecular analysis. Results Osthole (10 mg/kg) markedly prevented TCP particles-induced osteoclastogenesis and bone resorption in a mouse calvarial model. Osthole also inhibited the decrease of serum osteocalcin level and calvarial alkaline phosphatase (ALP) activity, and prevented the increase in the activity of tartrate resistant acid phosphatase (TRAP) and cathepsin K in the mouse calvaria. Furthermore, osthole obviously reduced the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) into the periosteum. Western blotting demonstrated TCP particles caused a remarkable endoplasmic reticulum (ER) stress response in the mouse calvaria, which was obviously blocked by osthole treatment. Conclusion These results suggest that local administration of osthole inhibits TCP particles-induced osteolysis in the mouse calvarial in vivo, which may be mediated by inhibition of the ER stress signaling pathway, and it will be developed as a new drug in the prevention and treatment of destructive diseases caused by prosthetic wear particles.