Titanium particle-induced osteogenic inhibition and bone destruction are mediated by the GSK-3β/β-catenin signal pathway

被引：38

作者：

Gu, Ye ^{[1
,2
]}

Wang, Zhirong ^{[3
]}

Shi, Jiawei ^{[1
]}

Wang, Liangliang ^{[1
]}

Hou, Zhenyang ^{[1
]}

Guo, Xiaobin ^{[1
]}

Tao, Yunxia ^{[1
]}

Wu, Xiexing ^{[1
]}

Zhou, Wei ^{[1
]}

Liu, Yu ^{[1
]}

Zhang, Wen ^{[4
]}

Xu, Yaozeng ^{[1
]}

Yang, Huilin ^{[1
]}

Xue, Feng ^{[2
]}

Geng, Dechun ^{[1
]}

机构：

[1] Soochow Univ, Affiliated Hosp 1, Dept Orthoped, 188 Shi Zi Rd, Suzhou 215006, Peoples R China

[2] Soochow Univ, Affiliated Peoples Hosp Changshou City 1, Dept Orthoped, Changshu, Jiangsu, Peoples R China

[3] Zhangjiagang Hosp Tradit Chinese Med, Dept Orthoped, Zhangjiagang, Peoples R China

[4] Soochow Univ, Orthoped Inst, Suzhou, Peoples R China

来源：

CELL DEATH & DISEASE | 2017年 / 8卷

关键词：

DIFFERENTIATING MC3T3-E1 CELLS; INDUCED OSTEOLYSIS; IN-VIVO; OSTEOCLAST DIFFERENTIATION; OSTEOPROGENITOR CELLS; SUPPRESSION; ACTIVATION; MICE; MASS; INFLAMMATION;

D O I：

10.1038/cddis.2017.275

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Wear debris-induced osteogenic inhibition and bone destruction are critical in the initiation of peri-prosthetic osteolysis. However, the molecular mechanism underlying this phenomenon is poorly understood. In this study, we analyzed the involvement of the GSK-3 beta/beta-catenin signal pathway, which is important for bone formation in this pathological condition. We established a titanium (Ti) particle-stressed murine MC3T3-E1 cell culture system and calvariae osteolysis model to test the hypothesis that Ti particle-induced osteogenic inhibition and bone destruction are mediated by the GSK-3 beta/beta-catenin signal pathway. Our findings showed that Ti particles reduced osteogenic differentiation induced by osteogenesis-related gene expression, alkaline phosphatase activity and matrix mineralization, as well as pSer9-GSK-3 beta expression and beta-catenin signal activity. Downregulation of GSK-3 beta activity attenuated Ti particle-induced osteogenic inhibition, whereas the beta-catenin inhibitor reversed this protective effect. Moreover, the GSK-3 beta/beta-catenin signal pathway mediated the upregulation of RANKL and downregulation of OPG in Ti particle-stressed MC3T3-E1 cells. In addition, our in vivo results showed that Ti particles induced bone loss via regulating GSK-3 beta and beta-catenin signals. Based on these results, we concluded that the GSK-3 beta/beta-catenin signal pathway mediates the adverse effects of Ti particles on osteoblast differentiation and bone destruction, and can be used as a potential therapeutic target for the treatment of peri-prosthetic osteolysis.

引用

页码：e2878 / e2878

页数：10

共 36 条

[1] The pathobiology and pathology of aseptic implant failure [J].

Athanasou, N. A. .

BONE & JOINT RESEARCH, 2016, 5 (05) :162-168

[2] The induction of a catabolic phenotype in human primary osteoblasts and osteocytes by polyethylene particles [J].

Atkins, Gerald J. ;

Welldon, Katie J. ;

Holding, Christopher A. ;

Haynes, David R. ;

Howie, Donald W. ;

Findlay, David M. .

BIOMATERIALS, 2009, 30 (22) :3672-3681

[3] Particle-Induced Osteolysis Is Mediated by TIRAP/Mal in Vitro and in Vivo Dependence on Adherent Pathogen-Associated Molecular Patterns [J].

Bechtel, Christopher P. ;

Gebhart, Jeremy J. ;

Tatro, Joscelyn M. ;

Kiss-Toth, Endre ;

Wilkinson, J. Mark ;

Greenfield, Edward M. .

JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 2016, 98 (04) :285-294

[4] Osteoclast differentiation and activation [J].

Boyle, WJ ;

Simonet, WS ;

Lacey, DL .

NATURE, 2003, 423 (6937) :337-342

[5] p38 signaling in titanium particle-induced MMP-2 secretion and activation in differentiating MC3T3-E1 cells [J].

Chen, Ming ;

Chen, Pei-Min ;

Dong, Qi-Rong ;

Huang, Qun ;

She, Chang ;

Xu, Wei .

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2014, 102 (08) :2824-2832

[6] Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice [J].

Clément-Lacroix, P ;

Ai, MR ;

Morvan, F ;

Roman-Roman, S ;

Vayssière, B ;

Belleville, C ;

Estrera, K ;

Warman, ML ;

Baron, R ;

Rawadi, G .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (48) :17406-17411

[7] Inhibition of osteolysis and increase of bone formation after local administration of siRNA-targeting RANK in a polyethylene particle-induced osteolysis model [J].

Cordova, L. A. ;

Trichet, V. ;

Escriou, V. ;

Rosset, P. ;

Amiaud, J. ;

Battaglia, S. ;

Charrier, C. ;

Berreur, M. ;

Brion, R. ;

Gouin, F. ;

Layrolle, P. ;

Passuti, N. ;

Heymann, D. .

ACTA BIOMATERIALIA, 2015, 13 :150-158

[8] Lack of β-catenin in early life induces abnormal glucose homeostasis in mice [J].

Dabernat, S. ;

Secrest, P. ;

Peuchant, E. ;

Moreau-Gaudry, F. ;

Dubus, P. ;

Sarvetnick, N. .

DIABETOLOGIA, 2009, 52 (08) :1608-1617

[9] Cartilage-specific β-catenin signaling regulates chondrocyte maturation, generation of ossification centers, and perichondrial bone formation during skeletal development [J].

Dao, Debbie Y. ;

Jonason, Jennifer H. ;

Zhang, Yongchun ;

Hsu, Wei ;

Chen, Di ;

Hilton, Matthew J. ;

O'Keefe, Regis J. .

JOURNAL OF BONE AND MINERAL RESEARCH, 2012, 27 (08) :1680-1694

[10] Primary Total Hip Arthroplasty with a Porous-Coated Acetabular Component A Concise Follow-up, at a Minimum of Twenty Years, of Previous Reports [J].

Della Valle, Craig J. ;

Mesko, Nathan W. ;

Quigley, Laura ;

Rosenberg, Aaron G. ;

Jacobs, Joshua J. ;

Galante, Jorge O. .

JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 2009, 91A (05) :1130-1135

← 1 2 3 4 →