Autophagy mediated CoCrMo particle-induced peri-implant osteolysis by promoting osteoblast apoptosis

被引：110

作者：

Wang, Zhenheng ^{[1
,2
,3
]}

Liu, Naicheng ^{[1
,2
,3
]}

Liu, Kang ^{[1
,2
,3
]}

Zhou, Gang ^{[1
,2
,3
]}

Gan, Jingjing ^{[1
,2
,3
]}

Wang, Zhenzhen ^{[1
,2
,3
]}

Shi, Tongguo ^{[1
,2
,3
]}

He, Wei ^{[1
,2
,3
]}

Wang, Lintao ^{[1
,2
,3
]}

Guo, Ting ^{[1
,2
,3
]}

Bao, Nirong ^{[1
]}

Wang, Rui ^{[1
]}

Huang, Zhen ^{[1
,2
,3
]}

Chen, Jiangning ^{[1
,2
,3
]}

Dong, Lei ^{[1
,2
,3
]}

Zhao, Jianning ^{[1
,2
,3
]}

Zhang, Junfeng ^{[1
,2
,3
,4
]}

机构：

[1] Nanjing Univ, Jinling Hosp, Dept Orthopaed, State Key Lab Pharmaceut Biotechnol, Nanjing 210008, Jiangsu, Peoples R China

[2] Nanjing Univ, Sch Med, Nanjing 210008, Jiangsu, Peoples R China

[3] Nanjing Univ, Sch Life Sci, Nanjing 210008, Jiangsu, Peoples R China

[4] Nanjing Univ, Jiangsu Prov Lab Nanotechnol, Nanjing 210008, Jiangsu, Peoples R China

来源：

AUTOPHAGY | 2015年 / 11卷 / 12期

基金：

国家高技术研究发展计划(863计划); 中国国家自然科学基金;

关键词：

aseptic loosening; autophagy; osteoblasts; osteolysis; wear particles; ENDOPLASMIC-RETICULUM STRESS; PARTICULATE WEAR DEBRIS; CELL-DEATH; PERIPROSTHETIC OSTEOLYSIS; TITANIUM PARTICLES; NANOPARTICLES; SUPPRESSION; HIP; BAX; OSTEOCLASTOGENESIS;

D O I：

10.1080/15548627.2015.1106779

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Wear particle-induced osteolysis is the leading cause of aseptic loosening, which is the most common reason for THA (total hip arthroplasty) failure and revision surgery. Although existing studies suggest that osteoblast apoptosis induced by wear debris is involved in aseptic loosening, the underlying mechanism linking wear particles to osteoblast apoptosis remains almost totally unknown. In the present study, we investigated the effect of autophagy on osteoblast apoptosis induced by CoCrMo metal particles (CoPs) in vitro and in a calvarial resorption animal model. Our study demonstrated that CoPs stimulated autophagy in osteoblasts and PIO (particle-induced osteolysis) animal models. Both autophagy inhibitor 3-MA (3-methyladenine) and siRNA of Atg5 could dramatically reduce CoPs-induced apoptosis in osteoblasts. Further, inhibition of autophagy with 3-MA ameliorated the severity of osteolysis in PIO animal models. Moreover, 3-MA also prevented osteoblast apoptosis in an antiautophagic way when tested in PIO model. Collectively, these results suggest that autophagy plays a key role in CoPs-induced osteolysis and that targeting autophagy-related pathways may represent a potential therapeutic approach for treating particle-induced peri-implant osteolysis.

引用

页码：2358 / 2369

页数：12

共 75 条

[1]

[Anonymous], TOXICOL APPL PHARM

[2] Screen for Chemical Modulators of Autophagy Reveals Novel Therapeutic Inhibitors of mTORC1 Signaling [J].