The cross-talk between osteoclasts and osteoblasts in response to strontium treatment: Involvement of osteoprotegerin
The cross-talk between osteoclasts and osteoblasts in response to strontium treatment: Involvement of osteoprotegerin
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DOI：
10.1016/j.bone.2011.08.031
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发表时间：
2011-12-01
期刊：
影响因子：
4.1
通讯作者：
Lu, W. William
中科院分区：
文献类型：
--
作者：
Peng, Songlin;Liu, X. Sherry;Lu, W. William
背景：锶对骨解偶联作用的机制尚不清楚。成骨细胞通过调节受体激活的核因子kappaB(RANK)配体(RANKL)和骨保护素(OPG)的表达，在破骨细胞的形成中发挥重要作用。我们推测OPG在锶对破骨细胞和成骨细胞之间的相互作用中起着重要作用。材料和方法：用氯化锶(0-3 mM)处理MC3T3E1细胞，并在处理后24小时收集条件培养液。通过抗酒石酸酸性磷酸酶(TRAP)染色和骨吸收陷窝分析评价条件培养液对破骨细胞形成的影响。实时荧光定量聚合酶链式反应检测成骨细胞中OPG和RANKL的表达，酶联免疫吸附试验检测条件培养液中蛋白质的分泌。在破骨前细胞中用抗OPG抗体进一步评价OPG在锶介导的抑制破骨细胞生成中的作用。通过动物实验评价了OPG在锶对骨质疏松骨解偶联作用中的作用。给去卵巢大鼠灌胃赋形剂或氯化锶2个月，同时加用抗Ig G抗体(对照组)或抗OPG抗体。结果：锶处理的成骨细胞条件培养液对破骨前细胞的破骨分化和骨吸收活性具有剂量依赖性的抑制作用。锶处理后，成骨细胞OPG mRNA表达和蛋白分泌明显增加。用抗OPG抗体中和后，条件培养液对RANKL诱导的破骨细胞生成的抑制作用消失。锶处理对松质骨的解偶联作用表现为较大的骨体积和骨小梁数量，较大的类骨质表面积和骨形成率，而较少的破骨细胞表面积。结论：体内外研究表明，OPG在锶对骨代谢的解偶联作用中起重要作用，其机制可能是作为破骨细胞和成骨细胞之间的一种串扰分子。(C)2011 Elsevier Inc.保留所有权利。
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.