The in vivo biological effects of intradiscal recombinant human bone morphogenetic protein-2 on the injured intervertebral disc -: An animal experiment

The in vivo biological effects of intradiscal recombinant human bone morphogenetic protein-2 on the injured intervertebral disc -: An animal experiment
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DOI:
10.1097/01.brs.0000263369.95182.19
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发表时间:
2007-05-15
期刊:
影响因子:
3
通讯作者:
Lin, Ruey-Mo
Lin, Ruey-Mo
中科院分区:
医学2区
文献类型:
--
作者:
Huang, Kuo-Yuan;Yan, Jing-Jou;Lin, Ruey-Mo

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研究设计:前瞻性分析。 目的:探讨重组人骨形态发生蛋白 -2(rhBMP -2)对纤维环撕裂后椎间盘的生物学影响。 背景资料概述:椎间盘损伤或退变的治疗效果不佳。rhBMP -2是一种高效的骨诱导和软骨诱导物质,已被批准用于前路腰椎椎间融合术。rhBMP -2在体外可刺激大鼠椎间盘细胞增殖和细胞外基质分泌。纤维环撕裂后椎间盘在体内的反应鲜有研究。 方法:20只新西兰白兔在L2 - L3、L3 - L4和L4 - L5节段分别接受全层纤维环撕裂,并向椎间盘内注射生理盐水(对照组)以及含或不含珊瑚移植物的0.1mg rhBMP -2。其中3只死亡或发生感染。因此,17只在12周时接受X线检查并被处死。脊柱切片用苏木精 - 伊红染色以检查对rhBMP -2的反应。 结果:X线片显示所有组均出现退变改变,如椎间隙变窄和不规则、软骨下硬化、骨赘形成以及椎体终板肥大。含珊瑚(P < 0.01)和不含珊瑚(P < 0.05)的rhBMP -2组退变比生理盐水组更频繁且更严重。2只接受rhBMP -2和珊瑚的兔子实现了坚固的椎间骨性融合。在2只对照组动物、3只接受rhBMP -2治疗的动物以及4只接受rhBMP -2和珊瑚治疗的动物中观察到新骨形成。与对照组(n = 3)相比,rhBMP -2组(n = 14)和含珊瑚的rhBMP -2组(n = 9)血管增多且成纤维细胞增殖增加(分别为P < 0.01和P = 0.03)。与对照组(n = 2)相比,rhBMP -2组(n = 8)炎症浸润增加(P = 0.03)。 结论:在影像学结果中,含或不含珊瑚的rhBMP -2治疗组退变改变更频繁且更严重。在组织病理学结果中,rhBMP -2促进了纤维环撕裂后椎间盘的血管增生和成纤维细胞增殖。
Study Design. Prospective analysis.Objective. To investigate biologic influences of recombinant human bone morphogenetic protein (rhBMP)-2 on intervertebral discs after anular tears.Summary of Background Data. Treatments for intervertebral disc injury or degeneration are unsatisfactory. rhBMP-2, a high-potency osteoinductive and chondro-inductive substance, is approved for use in anterior lumbar interbody fusions. rhBMP-2 stimulates the proliferation of rat disc cells and the secretion of extracellular matrix in vitro. In vivo responses in the intervertebral disc after anular tears are rarely studied.Methods. Twenty New Zealand white rabbits received full- thickness anular tears and intradiscal injections of saline (control) and rhBMP-20.1 mg with and without coral grafts at L2-L3, L3-L4, and L4-L5, respectively. Three died or had infection. Therefore, 17 underwent radiography and sacrifice at 12 weeks. Spinal sections were stained with hematoxylin and eosin to examine responses to rhBMP-2.Results. Radiographs revealed degenerative changes, such as disc space narrowing and irregularity, subchondral sclerosis, osteophyte formation, and hypertrophy of vertebral endplates in all groups. Degeneration was more frequent and severe with rhBMP-2 with (P < 0.01) and without ( P < 0.05) coral than with saline. Two rabbits receiving rhBMP-2 and coral achieved solid interbody bony fusion. New bone formation was noted in 2 controls, in 3 animals treated with rhBMP-2, and in 4 treated with rhBMP-2 and coral. Vascularity and fibroblast proliferation increased with rhBMP-2 (n = 14) and rhBMP-2 with coral (n = 9) compared with control (n = 3; P < 0.01 and P = 0.03, respectively). Inflammatory infiltrates increased with rhBMP-2 (n = 8) compared with control (n = 2; P = 0.03).Conclusions. Degenerative changes were more frequent and severe in the groups treated with rhBMP-2 with or without coral in radiographic findings. In histopathologic findings, rhBMP-2 promoted hypervascularity and fibroblast proliferation of the intervertebral disc after an anular tear.