The cross-talk between osteoclasts and osteoblasts in response to strontium treatment: Involvement of osteoprotegerin

被引：148

作者：

Peng, Songlin ^{[1
,3
]}

Liu, X. Sherry ^{[2
]}

Huang, Shishu ^{[3
]}

Li, Zhaoyang ^{[3
]}

Pan, Haobo ^{[3
]}

Zhen, Wanxin ^{[1
]}

Luk, K. D. K. ^{[3
]}

Guo, X. Edward ^{[4
]}

Lu, W. William ^{[3
]}

机构：

[1] Jinan Univ Sch Med, Shenzhen Peoples Hosp, Dept Spine Surg, Shenzhen, Peoples R China

[2] Columbia Univ, Dept Med, Div Endocrinol, New York, NY USA

[3] Univ Hong Kong, Dept Orthopaed & Traumatol, Hong Kong, Hong Kong, Peoples R China

[4] Columbia Univ, Dept Biomed Engn, Bone Bioengn Lab, New York, NY USA

来源：

BONE | 2011年 / 49卷 / 06期

基金：

美国国家卫生研究院;

关键词：

Strontium; Osteoblasts; Osteoclasts; Osteoprotegerin; Osteoporosis; MAINTAINING BONE-FORMATION; CALCIUM-SENSING RECEPTOR; TUMOR-NECROSIS-FACTOR; MARROW STROMAL CELLS; RESORPTION IN-VITRO; NONVERTEBRAL FRACTURES; RANELATE; DIFFERENTIATION; ACTIVATION; LIGAND;

D O I：

10.1016/j.bone.2011.08.031

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Background: The mechanism for the uncoupling effects of Sr on bone remains to be evaluated. Osteoblasts play important roles in osteoclastogenesis through regulating receptor activated nuclear factor kappa B (RANK) ligand (RANKL) and osteoprotegerin (OPG) expression. We hypothesize that OPG plays an important role in the cross-talk between osteoclasts and osteoblasts in response to Sr treatment. Materials and methods: MC3T3E1 cells were treated with Sr chloride (0-3 mM) and conditioned media were collected at 24 h after the treatment. The effect of conditioned media on osteoclastogenesis was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and bone resorption pits analysis. OPG and RANKL mRNA expressions in osteoblastic cells and protein secretion in the conditioned media were analyzed with real-time PCR and ELISA assay, respectively. The role of OPG in Sr-mediated inhibition of osteoclastogenesis was further evaluated with anti-OPG antibody in pre-osteoclastic cells. The role of OPG in Sr-mediated uncoupling effects on osteoporotic bone was evaluated by an animal study. Ovariectomized rats were oral administrated with vehicle or Sr chloride for two months supplemented with anti-IgG antibody (control) or anti-OPG antibody. The effects of OPG neutralization after Sr treatment on bone metabolism were analyzed by microCT, bone histomorphometry and biochemical analysis. Results: The conditioned media derived from Sr-treated osteoblastic cells exerted a dose-dependent inhibitory effect on osteoclastic differentiation and resorptive activity in pre-osteoclastic cells. OPG mRNA expression and protein secretion in osteoblastic cells were significantly increased after Sr treatment. Neutralization with anti-OPG antibody abolished the inhibitory effect of conditioned media on RANKL-induced osteoclastogenesis. The uncoupling effects of Sr treatment on trabecular bone were evidenced by greater bone volume and trabecular number, greater osteoid surface and bone formation rate, while less osteoclast surface. These effects were attenuated by the OPG neutralization by anti-OPG antibody injection. Conclusion: The evidences from the in vitro and in vivo studies suggested that OPG played an important role in the uncoupling effect of Sr on bone metabolism, possibly by acting as a cross-talk molecule between osteoclasts and osteoblasts in response to Sr treatment. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：1290 / 1298

页数：9

共 32 条

[1]

Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response [J].