Erythropoietin stimulates bone formation, cell proliferation, and angiogenesis in a femoral segmental defect model in mice
Erythropoietin stimulates bone formation, cell proliferation, and angiogenesis in a femoral segmental defect model in mice
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DOI：
10.1016/j.bone.2011.08.004
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发表时间：
2011-11-01
期刊：
影响因子：
4.1
通讯作者：
Menger, M. D.
中科院分区：
文献类型：
--
作者：
Holstein, J. H.;Orth, M.;Menger, M. D.
糖蛋白促红细胞生成素（EPO）已被证明可以促进骨折愈合。本研究的目的是探讨EPO治疗对股骨节段缺损模型骨修复的影响。研究了EPO （500 IE/kg/d）腹腔注射组（n = 38）和对照组（n = 40）的骨修复情况。在制造1.8 mm股骨节段缺损2周和10周后，通过显微ct、组织学和Western blot分析研究骨修复。10周时，显微ct和组织形态学分析显示，epo处理动物的骨缺损桥接率明显高于对照组。这与epo处理过的动物节段性缺损内显著较高的骨体积有关。在2周时，Western blot分析显示，与对照组相比，epo处理的动物血管内皮生长因子（VEGF）的表达显著增加。因此，在2周时，EPO组血管数量明显增加。在第10周，我们发现epo处理动物的增殖细胞核抗原（PCNA）的表达明显高于对照组。Western blot分析显示，内皮型和诱导型一氧化氮合酶（eNOS和iNOS）以及血管生成素受体Tie-2的表达在各组之间无显著差异。免疫组织化学证实了Western blot分析的结果，在第2周和第10周，epo处理动物的VEGF和pcna阳性细胞数量明显高于对照组。我们得出结论，EPO能够刺激股骨节段缺损模型中的骨形成、细胞增殖和vegf介导的血管生成。(C) 2011爱思唯尔公司版权所有。
The glycoprotein erythropoietin (EPO) has been demonstrated to stimulate fracture healing. The aim of the present study was to investigate the effect of EPO treatment on bone repair in a femoral segmental defect model. Bone repair was analyzed in mice which were treated by EPO (500 IE/kg/d intraperitoneally; n = 38) and in mice which received the vehicle for control (n = 40). Two and 10 weeks after creating a 1.8 mm femoral segmental defect, bone repair was studied by micro-CT, histology, and Western blot analysis. At 10 weeks, micro-CT and histomorphometric analyses showed a significantly higher bridging rate of the bone defects in EPO-treated animals than in controls. This was associated by a significantly higher bone volume within the segmental defects of the EPO-treated animals. At 2 weeks, Western blot analyses revealed a significantly higher expression of vascular endothelial growth factor (VEGF) in EPO-treated animals compared to controls. Accordingly, the number of blood vessels was significantly increased in the EPO group at 2 weeks. At 10 weeks, we found a significantly higher expression of proliferating cell nuclear antigen (PCNA) in EPO-treated animals when compared to controls. Western blot analyses showed no significant differences between the groups in the expression of the endothelial and inducible nitric oxide synthases (eNOS and iNOS) and the angiopoietin receptor Tie-2. Immunohistochemistry confirmed the results of the Western blot analyses, demonstrating a significantly higher number of VEGF- and PCNA-positive cells in EPO-treated animals than in controls at 2 and 10 weeks, respectively. We conclude that EPO is capable of stimulating bone formation, cell proliferation and VEGF-mediated angiogenesis in a femoral segmental defect model. (C) 2011 Elsevier Inc. All rights reserved.