Manipulation of the anabolic and catabolic responses with BMP-2 and zoledronic acid in a rat femoral fracture model
Manipulation of the anabolic and catabolic responses with BMP-2 and zoledronic acid in a rat femoral fracture model
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DOI：
10.1016/j.bone.2011.07.005
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发表时间：
2011-10-01
期刊：
影响因子：
4.1
通讯作者：
Tsumura, Hiroshi
中科院分区：
文献类型：
--
作者：
Doi, Yuji;Miyazaki, Masashi;Tsumura, Hiroshi
骨修复涉及一组复杂的调控信号通路，其控制新骨基质的形成和骨折部位受损骨基质的再吸收。据报道，单剂量唑来膦酸（ZA）给药的最佳时间点全身增加骨形态发生蛋白（BMP）-7介导的骨痂的强度。然而，其在骨折愈合过程中的修复机制仍不清楚。我们的目的是研究重组人（rh）BMP-2和ZA在大鼠股骨骨折模型中的协同作用。将58只大鼠分为4组。组I（n = 14）动物仅植入载体。组II（n = 15）动物植入含有1 μ g rhBMP-2的载体。第III组（n = 14）动物植入载体，并在手术后2周皮下全身注射ZA。IV组（n = 15）动物在术后2周皮下注射含1 μ g rhBMP-2和ZA的载体。6周后将大鼠安乐死，并将其骨折的股骨固定并通过手动触诊进行评估。X线照片和高分辨率显微计算机断层扫描（micro-CT），并进行生物力学和组织学分析。第IV组（93.3%）的融合率显著高于第I组（28.6%）、第II组（53.3%）和第III组（57.1%）。此外，第IV组的影像学评分高于第I、II和III组。在显微CT分析中，第IV组骨痂的组织体积（TV）高于第I组和第II组（p
Bone repair 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 fracture site. It has been reported that the optimal time point for single-dose zoledronic acid (ZA) administration systemically increased the strength of bone morphogenetic protein (BMP)-7-mediated callus. However, its repair mechanism during bone fracture healing remains unknown. We aimed to investigate the synergic effect of recombinant human (rh) BMP-2 and ZA in a rat femoral fracture model. Fifty-eight rats were divided into 4 groups. Group I (n = 14) animals were implanted with a carrier alone. Group II (n = 15) animals were implanted with a carrier containing 1-mu g rhBMP-2. Group III (n = 14) animals were implanted with a carrier and a subcutaneous systemic ZA injection 2 weeks after surgery. Group IV (n = 15) animals were implanted with a carrier containing 1-mu g rhBMP-2 and ZA subcutaneous injection 2 weeks after surgery. The rats were euthanized after 6 weeks and their fractured femurs were explanted and assessed by manual palpation. radiographs, and high-resolution micro-computerized tomography (micro-CT) and were subjected to biomechanical and histological analysis. The fusion rates in Group IV (93.3%) were considerably higher than those in Groups I (28.6%), II (53.3%), and III (57.1%). Additionally, the radiographic scores of Group IV were higher than those in Groups I, II, and III. In micro-CT analysis, the tissue volume (TV) of the callus was higher in Group IV than in Groups I and II (p