Manipulation of anabolic and catabolic responses with bone morphogenetic protein and zoledronic acid in a rat spinal fusion model

Manipulation of anabolic and catabolic responses with bone morphogenetic protein and zoledronic acid in a rat spinal fusion model
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DOI:
10.1016/j.bone.2013.09.021
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发表时间:
2014-01-01
期刊:
影响因子:
4.1
通讯作者:
Tsumura, Hiroshi
Tsumura, Hiroshi
中科院分区:
医学2区
文献类型:
--
作者:
Kodera, Ryuzo;Miyazaki, Masashi;Tsumura, Hiroshi

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骨融合涉及一组复杂的调控信号通路,其控制新骨基质的形成和手术部位受损骨基质的再吸收。据报道,在最佳时间全身给予单剂量的唑来膦酸(ZA)可增加骨形态发生蛋白(BMP)介导的骨痂的强度。在本研究中,我们的目的是研究BMP-2和ZA在大鼠脊髓模型中的作用。将67只大鼠分为6组:I组(n = 11)动物仅植入载体,II组(n = 12)动物植入载体并在手术后2周皮下注射ZA,III组(n = 12)动物植入含有1 μ g rhBMP-2的载体,IV组(n = 12)动物植入含有1 μ g rhBMP-2的载体,手术后2周皮下注射ZA,V组(n = 10)动物植入含有3 μ g rhBMP-2的载体,VI组(n = 10)动物植入含3 μ g rhBMP-2的载体,术后2周皮下注射ZA。6周后将大鼠安乐死,并通过手动触诊、X射线照相、高分辨率微型计算机断层扫描(micro-CT)和组织学分析对它们的脊柱进行检查和评估。VI组融合率(60%)明显高于I组(0%)、II组(0%)、III组(12.5%)、IV组(20.8%)和V组(35%)(P
Bone fusion involves a complex set of regulated signaling pathways that control the formation of new bone matrix and the resorption of damaged bone matrix at the surgical site. It has been reported that systemically administering a single dose of zoledronic acid (ZA) at the optimal time increases the strength of the bone morphogenetic protein (BMP)-mediated callus. In the present study, we aimed to investigate the effect of BMP-2 and ZA in a rat spinal model. Sixty-seven rats were divided into 6 groups: group I (n = 11) animals were implanted with a carrier alone, group II (n = 12) animals were implanted with a carrier and a subcutaneous injection of ZA was administered 2 weeks after surgery, group III (n = 12) animals were implanted with a carrier containing 1 jig of rhBMP-2, group IV (n = 12) animals were implanted with a carrier containing 1 mu g of rhBMP-2 and a subcutaneous injection of ZA was administered 2 weeks after surgery, group V (n = 10) animals were implanted with a carrier containing 3 mu g of rhBMP-2, and group VI (n = 10) animals were implanted with a carrier containing 3 mu g of rhBMP-2 and a subcutaneous injection of ZA was administered 2 weeks after surgery. The rats were euthanized after 6 weeks, and their spines were explanted and assessed by manual palpation, radiography, high-resolution micro-computerized tomography (micro-CT), and histologic analysis. The fusion rates in group VI (60%) were considerably higher than those in the groups I (0%), II (0%), III (12.5%), IV (20.8%), and V (35%), (P